In the present work, we have described the effects of serotonin (5-HT) depletion after the administration of 5,7-dihydroxytryptamine (5,7-DHT) into the median raphe nucleus in rats submitted to the pilocarpine model of epilepsy. 
Changes in 5-HT(1A) receptor-mediated neurotransmission at the level of the median raphe nucleus (MRN) are reported to affect the expression of defensive responses that are associated with generalized anxiety disorder (e.g.
Infusions of CRF (0.5 microg/0.5 microL) were made into the dorsal raphe nucleus of urethane-anesthetized rats following either inactivation of the median raphe nucleus by muscimol (25 ng/0.25 microL) or antagonism of CRF receptor type 1 or CRF receptor type 2 in the dorsal raphe nucleus with antalarmin (25-50 ng/0.5 microL) or antisauvagine-30 (2 microg/0.5 microL), respectively. Increased medial prefrontal cortex serotonin release elicited by CRF infusion into the dorsal raphe nucleus was abolished by inactivation of the median raphe nucleus.
We present an overview of our studies on the differential role of serotonergic projections from the median raphe nucleus (MRN) and dorsal raphe nucleus (DRN) in behavioural animal models with relevance to schizophrenia.
Mice received stereotaxic micro-injections of the serotonin neurotoxin 5,7-dihydroxytryptamine into the median raphe nucleus (MRN).
In the present study, we examined the role of corticotropin releasing factor (CRF) in the median raphe nucleus (MRN) on fear-related behaviors in rats.
This study explored the putative role of the principal 5-hydroxytryptamine (5-HT) neurones that project to the hippocampus from the median raphe nucleus in this response to an aversive environment by lesioning the 5-HT fibres that project through the fornix/fimbria and cingulum bundles. It is concluded that exposure to an explicitly aversive environment elicits a brief stimulation of the 5-HT neurones that project to the hippocampus from the median raphe nucleus and that this stimulation inhibits the initial burst of exploratory activity that is observed in animals placed in a less aversive novel environment..
rats with duration of a freezing response one standard error, or more, below the mean value, had a higher activity of the M2 cortical area, and the median raphe nucleus (c-Fox expression), in comparison to the high responders (HR), i.e.
RATIONALE AND OBJECTIVES: We previously found that the inhibition of median raphe nucleus (MRN) 5-HT transmission by local injections of a 5-HT1A agonist 8-OH-DPAT or corticotrophin-releasing factor (CRF) mimic the effect of foot shock stress to reinstate alcohol seeking.
We evaluated the involvement of dorsal hippocampus (DH) 5-HT1A receptors in the mediation of the behavioral effects caused by the pharmacological manipulation of 5-HT neurons in the median raphe nucleus (MRN).
RESULTS: A decrease in serotonin transporter density was detected in some frontal rat brain areas, and an increase in serotonin transporter density was detected in the right median raphe nucleus.
The effect of the equimolar doses (6, 20 and 60 nmol) of either adrenaline (AD) or noradrenaline (NA) microinjected into the median raphe nucleus (MR) on feeding behavior of food-restricted rats (15 g/day/rat) was investigated.
Finally, we also describe median raphe nucleus double-labeled cells (DY+TB) signaling diffuse descending projections for this largely studied nucleus that are involved in endogenous analgesia..
Here, we used extracellular single unit recording in midbrain slices to examine glutamate receptor mediated effects on 5-HT neuronal activity in the dorsal raphe nucleus (DRN) and the median raphe nucleus (MRN).
5-HT immunoreactivity in the dorsal raphe nucleus and the median raphe nucleus was also similarly detected in both animal groups.
Most serotonergic innervation of the forebrain arises from the median raphe nucleus (MRN) and dorsal raphe nucleus (DRN).
Serotonin 1A (5-HT1A) receptors are distributed throughout the brain with their highest concentrations in the frontal cortex, subthalamic nucleus and entopeduncular nucleus as well as the dorsal and median raphe nucleus.
Orexin-A or orexin-B was infused by reverse microdialysis into the dorsal raphe nucleus or median raphe nucleus of freely behaving rats, and extracellular serotonin was simultaneously collected by microdialysis and analyzed by high-performance liquid chromatography. We have found that orexin-A produced a dose-dependent increase of serotonin in the dorsal raphe nucleus, but not in the median raphe nucleus. However, orexin-B elicited a small but significant effect in both the dorsal raphe nucleus and median raphe nucleus.
The mesencephalic dorsal and median raphe nucleus (DRN; MRN) and three prosencephalic areas closely related to cognitive abilities (CA1 hippocampal area, striatum and frontal cortex) were studied by digital image analysis.
The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that receives a dense serotonergic innervation from the median raphe nucleus.
5-HT neurones in the median raphe nucleus (MRN) are involved in anxiety and the sleep/wake cycle.
The aim of this study was to investigate possible role of 5-HT(1A) and 5-HT(2) receptors in dorsal and median raphe nucleus on development of tolerance to analgesic effect of morphine using hot plate test. Chronic injection of 5-HT(1A) receptor agonist 8-OH-DPAT (8-hydroxy-2-[ di-n-propylamino]tetralin) (2, 4 and 8 mug/rat/day) to dorsal raphe nucleus (DRN) delayed tolerance to morphine analgesia, whereas injection of the same doses of 8-OH-DPAT to the median raphe nucleus (MRN) did not alter tolerance to morphine.
Brainstem serotonergic systems in the dorsal raphe nucleus and median raphe nucleus may be part of a distributed neural system that, together with the basolateral amygdala, regulates acute and chronic anxiety states. We therefore investigated the effect of an acute bilateral injection of urocortin 1 into the basolateral amygdala on behavior in the social interaction test and on c-Fos expression within serotonergic neurons in the dorsal raphe nucleus and median raphe nucleus. In home cage rats and rats exposed to the social interaction test, urocortin 1 treatment increased the number of c-Fos-immunoreactive serotonergic neurons within subdivisions of both the dorsal raphe nucleus and median raphe nucleus.
LTP was also blocked in anesthetized animals by direct application of WAY to the dentate gyrus, but not to the median raphe nucleus (MRN), suggesting the effect of systemic WAY is mediated by a block of dentate 5-HT1a receptors.
In male Sprague-Dawley rats, selected parts of the brain 5-HT systems were lesioned by micro-injection of the 5-HT neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus (DRN) or median raphe nucleus (MRN).
Mouse Ucn 2 had no effect on c-Fos expression within the median raphe nucleus, consistent with the hypothesis that Ucn 2 has specific actions on an anatomically and functionally distinct subset of serotonergic neurons via activation of CRF2 receptors.
The present investigation used single and multiple label tract tracing and immunofluorescence methods to evaluate the relative locations of the neuron groups and to compare them with the distributions of the three major afferent projections, the retinohypothalamic tract, geniculohypothalamic tract and the serotonergic pathway from the median raphe nucleus.
The IGL also provides a major input to the SCN, with a third major SCN afferent projection arriving from the median raphe nucleus.
The median raphe nucleus and dorsal raphe nucleus together are the major source of ascending 5-HT projections. Here, using in vitro extracellular single unit electrophysiology we examined the responses of individual neurones in the rat median raphe nucleus and dorsal raphe nucleus to alpha(1)-adrenoceptor and 5-HT(1A) receptor activation and made comparisons between the two nuclei. Compared to those in the dorsal raphe nucleus, the neurones in the median raphe nucleus which were inhibited by 5-HT had: (1) lower basal firing rates in the continuous presence of phenylephrine (1microM), (2) smaller excitatory responses to higher concentrations of phenylephrine (3-10microM), (3) smaller excitatory responses to brief application of norepinephrine (10-100microM) and (4) smaller inhibitory responses to 5-HT (10-50microM).
We detected strong hybridization signals in cell bodies located in the internal plexiform layer of the olfactory bulb, the interpeduncular nucleus of the midbrain, the ventral and dorsal tegmental nuclei, the median raphe nucleus of the pons, the ventral part of the medullary reticular nucleus, the ventral horn in the spinal cord of both rats and mice, and in a few Purkinje cells of rats, but not of mice.
The median raphe nucleus (MRN), which contains a major population of serotonin neurons, has also been implicated in freezing, but the serotonin neurons themselves do not seem to be involved, leaving it uncertain which neurons in this area promote freezing.
TPH2 mRNA is confirmed as the raphe-specific isoform of TPH in human brain, and is expressed in neurons throughout the anteroposterior extent of the DRN and median raphe nucleus (MRN).
Several studies have shown that the median raphe nucleus (MRN) is involved in anxiety.
Tryptophan hydroxylase immunoreactivity was increased in the median raphe nucleus at 2-3 weeks.
We have previously shown that brain serotonin depletion by lesions of the median raphe nucleus (MRN) causes enhancement of phencyclidine-induced locomotor hyperactivity [ S.
Estrogen receptors have been identified in the median raphe nucleus (MRN).
The median raphe nucleus (MRN) is the primary source of serotonergic afferents to the limbic system that are generally considered to suppress hippocampal theta oscillations.
GIR mRNA showed widespread distribution in forebrain limbic and thalamic structures, and a more restricted distribution in hindbrain areas such as the spinal trigeminal nucleus and the median raphe nucleus.
Serotonergic neurons in the mesencephalic median raphe nucleus (MnR) also give rise to a major SCN afferent projection.
In contrast, neither a phase shift nor estradiol altered the number of Fos-immunoreactive cells or the proportion of Fos-positive 5-HT cells in the median raphe nucleus.
Inhibition of the median raphe nucleus (MRN) by the local injection of 5-HT(1A) or GABA(A) receptor agonists produces strong activational effects on feeding, drinking and locomotor activity.
The following areas were studied: dorsal raphe nucleus (DRN); median raphe nucleus (MRN); thalamus; hypothalamus; amygdala, and hippocampus.
A single dose of CP-93,129 caused a significant increase in the synthesis in the median raphe nucleus (MR) without a significant influence on the dorsal raphe nucleus (DR).
RATIONALE: A wealth of evidence supports the involvement of the serotonergic neurons of the median raphe nucleus (MRN) in anxiety.
We have previously shown that lesions of the median raphe nucleus, but not the dorsal raphe nucleus, produced a marked enhancement of locomotor hyperactivity induced by phencyclidine and disruption of prepulse inhibition. The dorsal and ventral hippocampus receive serotonin projections predominantly from the median raphe nucleus and dorsal raphe nucleus, respectively. These results suggest that serotonin projections from the median raphe nucleus to the dorsal hippocampus play an important role in locomotor hyperactivity and prepulse inhibition in rats, animal models of aspects of schizophrenia.
RATIONALE: Intra-median raphe nucleus (MRN) administration of the 5-HT(1A) receptor agonist 8-OH-DPAT decreases lateral hypothalamic self-stimulation thresholds and is reported to have biphasic effects following systemic administration.
The cell bodies of 5-HT containing neurons that innervate the limbic forebrain are mainly found in the dorsal raphe nucleus and in the median raphe nucleus (MRN). To assess the role of the median raphe nucleus in anxiety, rats bearing either electrolytic or 5-HT-selective neurotoxic lesion of the MRN were tested in the elevated T-maze.
Non-photic cues are notably conveyed to the SCN by a direct 5-HT pathway arising from the mesencephalic median raphe nucleus (MRN).
It has previously been shown that the median raphe nucleus (MR) is one of the main sources of projections to the septum and hippocampus.
Serotonergic median raphe nucleus and noradrenergic locus ceruleus act as functional antagonists in theta regulation: the former structure restricts the theta rhythm generation, whereas the latter enhances this process.
The mGlu1 receptor is also present in variable degree in the dorsal lateral septal nucleus, amygdala, interpeduncular nucleus and median raphe nucleus.
Other VGLUT3-positive boutons immunopositive for serotonergic markers but negative for GAD probably originate from the median raphe nucleus and innervate select interneurons.
The median raphe nucleus is involved in controlling and maintaining hippocampal activity through its projection to inhibitory neurons in medial septum and hippocampus. It has been shown that anterogradely axonal-traced fibers originating in the median raphe nucleus project onto calbindin-containing neurons in hippocampus and parvalbumin-containing neurons in medial septum. However, in both dorsal and median raphe nucleus there is a large amount of non-serotonergic neurons which also are projecting neurons, indicating that a part of the raphe fibers projecting to hippocampus and septum may be non-serotonergic. Biotin dextran amine was used as the anterograde neuronal tracer and injected into either dorsal or median raphe nucleus.
The pre-frontal and cingulate cortex, median raphe nucleus, septum and hippocampus seem to be implicated in the elaboration and organization of these responses.
Since rats with electrolytic lesion in the area of the median raphe nucleus displayed high frequencies of HD in a previous study, the present investigation was undertaken to confirm this observation and to determine its anxiety-related origin.
A single IMO elicited a threefold rise in TPH mRNA in median raphe nucleus (MRN), but repeated (3x) IMOs were needed for similar response in dorsal raphe nucleus (DRN).
Dorsal and median raphe nucleus (DRN and MRN), hippocampus (Hipp), striatum (Strt) and frontal cortex (FCx) were studied by computer-assisted image analysis.
The expression of Fos protein in 5-HT-containing neurons (5-HT/Fos co-localized neurons) could be observed in the ventrolateral subdivision of the midbrain periaqueductal grey, interpeduncular nucleus, paramedian raphe nucleus, all of the brainstem raphe nuclei, the alpha part of the gigantocellular reticular nucleus and the lateral paragigantocellular reticular nucleus. However, the number and proportion of the 5-HT/Fos co-localized neurons in the median raphe nucleus and nucleus raphe obscurus of the rat subjected to visceral noxious stimulation were statistically greater than those in rats subjected to somatic noxious stimulation. These results suggest that serotonergic neurons in median raphe nucleus and nucleus raphe obscurus have a tendency to higher neuronal activity after visceral noxious stimulation..
In earlier studies it has been shown that stimulation of the median raphe nucleus (MR) in awake rabbits decreases the expression and frequency of oscillatory theta activity in the septohippocampal system, and the functional blockade of this nucleus evokes the regular and high-frequency theta rhythm.
We used double-label in situ hybridization to examine the cellular localization of 5-ht(5B) receptor mRNA in relation to serotonin transporter mRNA in the rat dorsal raphe (DR) and central superior nucleus (CS, median raphe nucleus).
A statistically significant reduction of 50.3%, together with a significant decrease of 53.94% in the density of serotoninergic neurons, was also observed in the median raphe nucleus as compared with control animals.
Using a rat relapse model, we have shown that infusion of a corticotropin-releasing factor (CRF) receptor antagonist into the median raphe nucleus (MRN) blocks footshock stress-induced reinstatement of alcohol seeking in rats.
Ascending 5-HT projections from the median raphe nucleus (MRN), probably to the hippocampus, are implicated in the acquisition of contextual fear (background stimuli), as assessed by freezing behavior.
Previously, we reported that electrical stimulation of the dorsal raphe nucleus (DRN) or median raphe nucleus (MRN) in hamsters evoked 5-HT release in the SCN.
Pentobarbital-anesthetized (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically microinjected with 1 microl of a 5 microg/microl solution of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into either the dorsal or median raphe nucleus.
Posterior 5HT cells (median raphe nucleus) innervate hippocampus and cingulate gyrus and suppress memory and awareness of current and past adversity.
In BDNF (+/-) versus wild-type (WT) mice, 5-HT1A receptor-stimulated [ 35S]GTP gamma S binding was significantly attenuated in the median raphe nucleus.
We have shown that 5-HT mechanisms of the median raphe nucleus (MRN) are involved in contextual fear-conditioning processes as electrolytic or neurotoxic lesions with N-methyl-D-aspartate (NMDA) or injections of 8-hydroxy-2-(di-n-propilamino)-tetralin (8-OH-DPAT) into this structure inhibit freezing behavior in a contextual fear paradigm.
Rats were injected intraperitoneally with either LPS (100 microg/kg) or IL-1 beta (2 microg/kg) at lights out, and 8-OH-DPAT (4 nmol) was administered directly into the median raphe nucleus at the onset of anorexia.
The effects of injecting testosterone propionate or estradiol benzoate to newborn rats on dopaminergic and serotoninergic activity in the frontal cortex, dorsal and median raphe nucleus were analyzed when animals reached adulthood. An increase in androgen or estrogen levels at birth caused a significant decrease in serotoninergic activity in the frontal cortex and in the dorsal raphe nucleus, without causing apparent changes in dopaminergic activity; serotinergic activity in the median raphe nucleus was not affected.
Considering the fact that median raphe nucleus (MRN) constitutes one of the inputs of the hippocampus, the effects of reversible inactivation of MRN on long-term potentiation (LTP) and recurrent inhibition in the dentate gyrus (DG) of rat hippocampus, in vivo, were examined.
The suprachiasmatic nucleus (SCN) receives its serotonergic input from the median raphe nucleus, while the intergeniculate leaflet (IGL) receives serotonergic innervation from the dorsal raphe nucleus (DRN).
Within the rostral brainstem cluster, three distinct divisions were found: the dorsal raphe nucleus (with four subdivisions), the median raphe nucleus and the cells of the supralemniscal region.
Serotonin (5-HT) neurons located in the median raphe nucleus (MRN) may have a role in the development of behavioral changes to stress.
To test this hypothesis, we used in vivo microdialysis to measure changes in extracellular serotonin (5-hydroxytryptamine; 5-HT) in response to local infusion of mu-, delta-, and kappa-opioid receptor ligands into the dorsal raphe nucleus (DRN), median raphe nucleus (MRN), and nucleus accumbens (NAcc) of freely behaving rats.
The aim of the present study was to investigate the effects of excitotoxic damage of the serotonergic cell bodies in the median raphe nucleus (MRN) on the scopolamine-induced working memory deficits in a single-trial light/dark inhibitory avoidance task.
Here we studied the role of the 5-HT cell body region of the median raphe nucleus (MRN) and CRF receptors in this site in reinstatement of alcohol seeking.
An age-related decrease in the maximal density of serotonin transporter sites labelled with [ (3)H]paroxetine (fmol/mg protein, Old: 396+/-13; Young: 487+/-27) was observed in the dorsal raphe nucleus (DRN) but not the median raphe nucleus (MRN), without affecting the affinity of [ (3)H]paroxetine.
The serotonin (5-HT)-containing median raphe nucleus has been shown to be critically involved in the control of desynchronized (non theta) states of the hippocampal electroencephalogram (EEG). We examined the activity of 181 cells of the median raphe nucleus in the urethane-anesthetized rat and found that approximately 80% (145/181) of them showed changes in activity associated with changes in the hippocampal EEG. A role for the median raphe nucleus in memory-associated functions of the hippocampus is discussed..
The interactions between the median raphe nucleus (MRN) serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated.
The experiments investigated the interactions between median raphe nucleus (MRN) serotonergic and septo-hippocampal muscarinic cholinergic systems in the modulation of forming and storing performances of working memory.
In addition, transsynaptic retrograde labeling was observed in cholinergic neurons in the horizontal limb of diagonal band, serotonergic neurons in the median raphe nucleus, and noradrenergic neurons in the locus coeruleus, all of which project centrifugal fibers to the olfactory bulb.
Electrical stimulation of the dorsal raphe nucleus (DRN) or median raphe nucleus (MRN) was performed in anaesthetised rats implanted with microdialysis probes in the hippocampus and locus coeruleus (LC).
Binding to NA transporters revealed increased densities in sensory nuclei of cranial nerves, granular layer of the cerebellar cortex, as well as in cerebellar-related and basal ganglia structures, such as the lateral cuneate nucleus, pontine nuclei, substantia nigra, pontine reticular formation, median raphe nucleus and superior colliculus.
However, with the chronical 2,4-D exposure (T2 group) only the 5-HT neuronal area from the dorsal raphe nucleus (DRN) was increased, suggesting an adaptable response of 5-HT neurons in median raphe nucleus (MRN).
5-HT neurons respond to acute sound stress within the median raphe nucleus (MRN), but not within the dorsal raphe nucleus or hindbrain regions.
These data suggest that ethanol may activate terminals of the median raphe 5-HT system in P rats because the vHIP receives its 5-HT inputs primarily from the median raphe nucleus (MRN).
Previous studies have shown that serotonergic neurons of the median raphe nucleus have a suppressive effect on theta synchronization in the hippocampus. We found that sustained infusion of the GABA(B) receptor agonist baclofen into the median raphe nucleus, using the microdialysis technique, elicited lasting theta activity in the hippocampus.
Sound stress increases 5-HTP accumulation in median raphe nucleus, hippocampus, cortex, and nucleus accumbens, but not dorsal raphe nucleus or caudate nucleus. In contrast, the morphine treatment enhances 5-HTP accumulation in dorsal raphe nucleus, cortex and caudate nucleus, but not in median raphe nucleus, hippocampus or nucleus accumbens. These findings provide further support for the presence of serotonergic neurons within the median raphe nucleus that have a unique response profile.
Experiments were performed with the inhibitory avoidance apparatus in rats with ibotenic acid lesions of the median raphe nucleus.
Some of these results are similar to those found in the human median raphe nucleus with the same methods..
We have shown that the median raphe nucleus (MRN) is involved in the control of contextual fear conditioning.
Performance of avoidance task increased Fos-like immunoreactivity in the medial amygdaloid nucleus, in the anterior hypothalamic nucleus and in the median raphe nucleus.
Here we examined the role of 5-HT1B receptors in the control of 5-HT output and firing in the dorsal raphe nucleus (DR), median raphe nucleus (MnR) and forebrain of the rat in vivo.
These results implicate 5-HT mechanisms of the median raphe nucleus in the regulation of anxiety and in the genesis of gastric stress ulcers..
Responses to sensory stimuli were analyzed in hippocampal CA1 neurons of unanesthetized rabbits in chronic experiments before and after reversible functional blockade of the median raphe nucleus (MR) and medial septal area (MS-DB) by local microinjections of anesthetic lidocaine.
In 5-HT(1B) receptor knockout mice, R-8-OH-DPAT evoked a significantly diminished response in the ventral hippocampus, but not the striatum, suggesting the potential desensitization of 5-HT(1A) receptors in the median raphe nucleus.
The 5-HT(1A) autoreceptor plays a larger role in regulating 5-HT release in the striatum and possibly other brain regions innervated by the dorsal raphe nucleus, whereas the role of the 5-HT(1B) receptor is relatively greater in the hippocampus and possibly other brain regions innervated by the median raphe nucleus..
Concomitantly, 5-HT(1A) mRNA expression was decreased by 13% in the ventrolateral part of the dorsal raphe nuclei, while no changes were found in the median raphe nucleus and entorhinal cortex.
In adult rats the hippocampal NGF content changed in a biphasic way after lesion of the median raphe nucleus by 5,7-dihydroxytryptamine (5,7-DHT), with a significant increase after 2-3 weeks of up to 35%, followed by a significant reduction of 22% below control levels after 7 weeks, and a return to control levels within the following 4 weeks. The present data indicate that a serotonergic lesion of the median raphe nucleus results in biphasic changes of NGF protein content and in a delayed increase in the vulnerability of septohippocampal cholinergic neurons..
In the acute treatment studies, WAY100635 (1 mg/kg) induced a significant increase in 5-HT synthesis in the median raphe nucleus and some nerve terminal structures (range between 18 and 53%), while WAY100135 (10 mg/kg) produced a significant decrease of synthesis, in the range between 16 and 33%, in the raphe magnus nucleus and several projection areas.
It has previously been shown that the median raphe nucleus (MR) is a source of pronounced projections to the septum and hippocampus. The fluorescent retrograde tracers, Fluororuby and Fluorogold, were injected into the septum and hippocampus, respectively, and the median raphe nucleus was examined for the presence of single- and double-labeled neurons.
To clarify the role of the preoptic area and anterior hypothalamus (PO/AH) on thermoregulatory system and the effects of serotonergic innervation from the median raphe nucleus (MRN) on body temperature (Tb), we perfused tetrodotoxin (TTX) solution into the PO/AH or MRN by using a microdialysis technique at different ambient temperatures (5, 23 and 35 degrees C) in freely moving rats.
ICSS induced a significant but different degree of increase in the number of Fos-immunopositive (Fos+) cells in the six brainstem monoaminergic nuclei examined, which included the ventral tegmental area (VTA), substantia nigra pars compacta (SNc), dorsal raphe nucleus (DR), median raphe nucleus (MR), locus coeruleus (LC), and A7 noradrenaline cells.
Allylnitrile induced changes in the immunolabelling of GABA in the medial habenula, interpeduncular nucleus, substantia nigra, dorsal raphe nucleus and median raphe nucleus; the amount of immunolabelling decreased in all of these brain structures except the medial habenula at 2 days postdosing, and increased in all of these structures at 14 days postdosing.
Rats with electrolytic lesions of the median raphe nucleus (MRN) were found to display a profound impairment in both the acquisition and retention of spatial memory task. In this study, the lidocaine inactivation was employed to evaluate the involvement of the rat's median raphe nucleus in reference and working memory versions of the Morris water maze (MWM) task.
Injections of muscimol into the median raphe nucleus (MR) elicit intense drinking in normally hydrated rats.
Flesinoxan infused either into the dorsal raphe nucleus or the median raphe nucleus did not affect startle potentiation.
It is known that the median raphe nucleus (MRN) is the origin of a serotonergic pathway and mainly innervates septo-hippocampal formation which plays an important role in emotional cognition. In the present study, the animals underwent ibotenic acid or sham lesions of the median raphe nucleus and the effects of MRN lesions on immediate and delayed fear conditioning to multiple contextual cues were studied.
The effect of electrolytic lesion of the median raphe nucleus was measured on behavioral and physiological parameters related to stress 24 h after the lesion. These results highlight the importance of the median raphe nucleus in the regulation of stress and anxiety.
Analysis of double-labelled sections revealed that almost half of the 5-HT neurons in the dorsal raphe and around 25% in the median raphe nucleus expressed substance P mRNA.
The purpose of the present study was to investigate the behavioral consequences and the neurochemical correlates of a 5,7-dihydroxytryptamine (5,7-DHT) lesion of the median raphe nucleus (MRN) in rats.
The 5-HT(1A/7) receptor agonist 8-hydroxy-2-[ di-n-propylamino]-tetralin (8-OH-DPAT) has chronobiological effects on the circadian system and, in the Syrian hamster, it is known that serotonergic (5-HT) projections connecting the median raphe nucleus to the suprachiasmatic nuclei (SCN) of the hypothalamus are a prerequisite for the expression of 8-OH-DPAT-induced phase advance of locomotor activity rhythm.
Spontaneous activity and responses to sensory stimuli were analysed in the hippocampal CA1 neurons of chronic unanesthetized rabbits before and after reversible functional blockade of the median raphe nucleus and medial septal area by local microinjections of anesthetic lidocaine. Intra-median raphe nucleus injection of lidocaine evoked uniform increase of discharge rate in the hippocampal neurons with low and high spontaneous activity. Comparison of spontaneous and evoked activity in two theta states (physostigmine and median raphe nucleus blockade) revealed striking similarity of all characteristics, which suggested that theta-suppressing influences of median raphe nucleus (presumably serotonergic) are realized primarily through the control of cholinergic septo-hippocampal theta-generating mechanism. However, as the frequency of theta rhythm does not depend on it, an additional effect of disinhibition of activating reticular formation by the median raphe nucleus suppression is suggested.
In the first series of experiments stimulating electrodes were implanted into the midbrain reticular formation and median raphe nucleus. The standard frequency of theta-bursts in medial septal area neurons and in the electroencephalogram was uniformly and chronically decreased in all rabbits with electrodes implanted into the median raphe nucleus (4.7 +/- 0.5 Hz versus 5.2 +/- 0.19 Hz in animals without electrodes in median raphe nucleus). Weak electrical stimulation of the median raphe nucleus resulted in additional decrease of theta expression in the medial septal area neurons and its disappearance from the hippocampal electroencephalogram, where it was substituted by delta-waves and spindles. In the second series of experiments reversible functional blockade of the median raphe nucleus by local microinjection of lidocaine was performed. It is concluded that, in accordance with the data of other authors, the median raphe nucleus can be regarded as a functional antagonist of the reticular formation, powerfully suppressing theta-bursts of the medial septal area neurons and hippocampal theta rhythm. It is suggested that, in combination with the theta-enhancing influences of reticular formation, the median raphe nucleus may participate in termination of attention, its switching to other stimuli and stabilization of the effects of learning..
In contrast, microinjection of WAY100635 in the median raphe nucleus did not alter the stimulant effect of cocaine on locomotor activity, rears or head bobs. It may be suggested from these results that stimulation of somatodendritic 5-HT1A autoreceptors located in the dorsal raphe nucleus mediates an inhibitory effect on cocaine-induced locomotor activity and head bobs, whereas somatodendritic 5-HT1A autoreceptors in the median raphe nucleus are not involved in the inhibitory role of 5-HT on the stimulant effect of cocaine on locomotor activity and head bobs.
It is argued that enhanced habituation must involve a different mechanism, such as enhanced 5-HT1A function in the terminal fields of the median raphe nucleus..
Brains from a female and a male newborn who died from an asphictic syndrome were examined to study the cytoarchitecture of the median raphe nucleus using the Golgi-Cox and morphometric methods.
The present study examined whether a potentiation of cocaine-induced behaviour in rats following peripheral pretreatment with the 5-hydroxytryptamine (5-HT) biosynthesis inhibitor p-chlorophenylalanine may be due to depletion of 5-HT in the dorsal raphe nucleus and/or median raphe nucleus. To investigate a possible involvement of serotonergic neurones arising in the midbrain raphe nuclei in the observed potentiation, p-chlorophenylalanine (0.5 microg) was microinjected in either the dorsal raphe nucleus or median raphe nucleus followed by behavioural testing 48 h later. In contrast, the stimulant effect of cocaine on behaviour was not altered by microinjection of p-chlorophenylalanine in the median raphe nucleus. Surprisingly, the central application of p-chlorophenylalanine in the dorsal raphe nucleus and median raphe nucleus did not alter the 5-HT levels in the midbrain raphe nucleus investigated. In conclusion, the behavioural results suggest that the potentiation of cocaine-induced behaviour following peripheral p-chlorophenylalanine administration may be attributed to the dorsal raphe nucleus but not the median raphe nucleus suggesting that, serotonergic dorsal raphe nucleus neurones may normally mediate a tonic inhibitory effect on cocaine-induced behaviour.
The aim of the present study was to determine, at the light microscopic level, whether the serotonergic fibers originating from the dorsal raphe nucleus (B7), median raphe nucleus (B8) and ventral tegmentum (B9) make putative synaptic contacts with cholinergic neurons of the nucleus basalis magnocellularis and substantia innominata. Following Phaseolus vulgaris leucoagglutinin injection in the median raphe nucleus, very few labeled fibers with no evident close contact with nucleus basalis magnocellularis and substantia innominata cholinergic neurons were observed.
The present study was conducted in order to examine the influence of catecholaminergic afferents on the release of serotonin in the median raphe nucleus in vivo. To this aim, selective dopamine D1 and D2, and alpha1- and alpha2-adrenergic agonists and antagonists were administered locally (1, 10 and 100 microM) through a dialysis probe implanted in the median raphe nucleus of freely moving rats. The D1 and D2 agonists, (+/-)-1-phenyl-2,3,4, 5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF-38393) and quinpirole, respectively, and the D1 and D2 antagonists, R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine (SCH-23390) and raclopride, respectively, did not alter the release of serotonin in the median raphe nucleus. These results indicate that the release of serotonin in the median raphe nucleus does not appear to be regulated by dopaminergic afferents through the activation of dopamine D1 or D2 receptors. On the contrary, it is suggested that endogenous noradrenaline exerts a direct tonic stimulatory control on the release of serotonin through alpha1-adrenoceptors, and an indirect tonic inhibitory influence through alpha2-adrenoceptors located probably in noradrenergic nerve terminals within the median raphe nucleus..
Repeated immobilization stress (2 h, 7 days) elicited a six- or ten-fold rise in TPH mRNA in median raphe nucleus (MRN) and dorsal raphe nucleus (DRN), respectively, without significantly altering TPH mRNA levels in the pineal gland.
Four neuroanatomical regions that regulate circadian timekeeping were studied (the suprachiasmatic nuclei [ SCN], the lateral geniculate nuclei [ LGN], and the median raphe nucleus [ MRN] and dorsal raphe nucleus [ DRN]).
The intergeniculate leaflet, which projects to the SCN via the geniculohypothalamic tract, receives serotonergic innervation from the dorsal raphe nucleus, and the SCN receives its serotonergic input from the median raphe nucleus.
Our results show that both interneuron-selective cells and vasoactive intestinal polypeptide-containing basket cells receive synaptic input from the medial septum and median raphe nucleus.
Norepinephrine levels were found to be two to threefold higher in the nucleus accumbens, prefrontal cortex, hippocampus and median raphe nucleus of FSL rats as compared with control Sprague-Dawley rats.
Image analysis of cells from B7, the dorsal raphe nucleus, and B8, the median raphe nucleus, revealed significant differences between groups in the mean cellular level of 5-hydroxytryptamine transporter gene expression.
Involvement of median raphe nucleus (MRN) in acquisition, consolidation and retrieval of passive avoidance (PA) was investigated with functional suppression of this area by lidocaine.
The 5-HT1A receptor agonist was infused into the median raphe nucleus (N = 60) and medial septal area (N = 68) 10 min before the test. The results showed that in the median raphe nucleus only the highest dose of 8-OH-DPAT (2.0 microg) increased the percentage of time spent on the open arms.
Sex steroids had no effect on the number of SERT mRNA-expressing cells in the median raphe nucleus.
The present study has examined several characteristics of the release of 5-HT in the median raphe nucleus in terms of its dependence of nerve impulse, provenance of a vesicular storage fraction as well as the regulatory role played by 5-HT1A receptors. These results indicate that extracellular 5-HT in the median raphe nucleus is stored in vesicles and released in an impulse-dependent manner. Also, the basal release of 5-HT in the median raphe nucleus does not appear to be under the tonic control of somatodendritic 5-HT1A receptors by endogenous 5-HT. Instead, this feedback mechanism seems to be triggered when an excess of the transmitter or a 5-HT1A agonist is present in the extracellular space of the median raphe nucleus..
The results demonstrate that serotonergic neurons in the median raphe nucleus contribute to the regulation of rhythm phase response to TRZ and that it is unlikely that these neurons are necessary for phase response to NW access.
The computer reconstructions demonstrated a 3-dimensional distinct pattern in the rostral pontine reticular formation, with high (3H)lysergic acid diethylamide binding to serotonin receptors in the median raphe nucleus flanked by paramedian bands of high (3H)quinuclidinyl benzilate binding to muscarinic cholinergic receptors in the medial nucleus pontis oralis.
The present study demonstrates that, in the Syrian hamster, the 5-HT fibres connecting the RN to the SCN are essential for the phase-shifting action of peripheral 8-OH-DPAT injections, and that the drug does very probably not exert its chronobiological effect directly onto SCN neurons but through receptors localized on median raphe nucleus neurons..
Two components of the circadian system, the suprachiasmatic nucleus (SCN) (site of the circadian clock) and the intergeniculate leaflet (IGL), receive serotonergic projections from the median raphe nucleus and the dorsal raphe nucleus, respectively.
To examine this possibility, we have conducted a regional microdialysis study in the DRN, MRN and four forebrain regions preferentially innervated either by the DRN (frontal cortex, striatum) or the median raphe nucleus (MRN; dorsal and ventral hippocampus) using freely moving rats.
Because the vHIP receives a major 5HT input from the median raphe nucleus (MRN), the results suggest that acute ethanol activates the MRN 5-HT system projecting to the vHIP and that rapid tolerance develops to the activating effects of alcohol on this pathway..
Statistically significant decreases (P < 0.05 and P < 0.02) in glucose utilization ranging from -15 to -26% were also displayed in the superior colliculus superficial layer, auditory cortex, ventroposterior nucleus of the thalamus, molecular layer of the hippocampus, dentate gyrus, medial amygdaloid nucleus, median raphe nucleus, subthalamic nucleus, medial preoptic area of the hypothalamus and anterior hypothalamus.
From the median raphe nucleus, a rostral projection ascended in the ventral part of the mesencephalon to continue in the medial forebrain bundle of the forebrain. Thus, this study of the golden hamster shows a serotonergic projection from the median raphe nucleus to the suprachiasmatic nucleus and a projection from the dorsal raphe nucleus to the deep pineal gland supporting physiological indications of an influence of serotonin on the photoreceptive circadian system of the brain..
Further rostrally, labeled cells were clustered bilaterally above the medial longitudinal fasciculi and extended into the median raphe nucleus.
Initial pathway tracing experiments using retrograde (horseradish peroxidase conjugates with wheatgerm agglutinin or choleratoxin B subunit) and anterograde (Phaseolus vulgaris-leucoagglutinin) markers demonstrated a direct, bilateral projection to the dorsal raphe nucleus and median raphe nucleus from the medial prefrontal cortex, and the origin of this projection was localized predominantly in the ventral medial prefrontal cortex (infralimbic/dorsal penduncular cortices). Using chloral hydrate-anaesthetized rats, extracellular recordings were made mostly from 5-hydroxytryptamine neurons in the dorsal raphe nucleus, but non-5-hydroxytryptamine dorsal raphe neurons were also studied, as was a small number of 5-hydroxytryptamine neurons in the median raphe nucleus.
A method of controlled successive short-term (25-30 min) stabilization or suppression of the theta rhythm by local injections of lidocaine into median raphe nucleus or medical septal area (MS-DB) was tested for further analysis of the functional significance of theta-modulation in activity of hippocampal neurons.
Since previous studies by others have indicated that the reserve of somatodendritic 5-HT1A receptors is greater in dorsal raphe nucleus innervating frontal cortex and striatum than in median raphe nucleus which mainly innervates hippocampus, the observed different regional potency of the two 5-HT1A receptor antagonists may be explained by this difference in the 5-HT1A receptor reserve..
The ability of both compounds to increase 5-HT levels in the dentate gyrus suggests a lack of 5-HT1B/1D receptors in the median raphe nucleus.
The median raphe nucleus (MRN) has been suggested as the origin of a behavioral inhibition system that projects to the septum and hippocampus. The animals underwent electrolytic or sham lesions of the median raphe nucleus. These results point to the importance of the median raphe nucleus in the processing of fear conditioning with freezing being the most salient feature of it.
These results suggest that serotonergic neurons in the median raphe nucleus play an inhibitory role in the regulation of male sexual activity, especially ejaculation.
The relationship between hippocampal activity and the extracellular level of excitatory amino acids in the median raphe nucleus has been studied in urethane anaesthetized rats, using the in vivo microdialysis technique. Dialysates were collected from the median raphe nucleus during two to eight sampling periods of equal length (20 min) and hippocampal electroencephalogram was continuously monitored. For each observation period, the average glutamate level in the median raphe nucleus was determined and the percentage of theta and non-theta segments in the hippocampal recordings was calculated. The relationship between hippocampal activity and glutamate release in the median raphe nucleus was characterized by comparison of the direction of changes in these two parameters in consecutive sampling periods. We found that as long as theta/non-theta ratio changed spontaneously or under the effect of anticholinesterase (n = 7), the extracellular level of glutamate in the median raphe nucleus was elevated during periods dominated by desynchronized hippocampal activity as compared with those mostly containing long and/or frequently occurring theta segments. Such relationship was not observed in the adjacent reticular formation (n = 4) and in the median raphe nucleus during sensory stimulation (n = 2). The present data complete those found earlier indicating that the desynchronizing serotonergic influence originating from the brainstem is maintained by a tonic excitatory input to the median raphe nucleus. Since the majority of glutamatergic afferents to the median raphe nucleus originates from the lateral habenula and the interpeduncular nucleus, known to connect limbic forebrain to the brainstem, theta associated changes in median raphe nucleus glutamate levels might reflect descending forebrain influences, suggesting therefore a feedback regulation of the hippocampal activity involving brainstem structures..
It is proposed that 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is more toxic to 5-HT neurones projecting from the dorsal raphe nucleus (DRN) than to those from the median raphe nucleus (MRN).
In vivo microdialysis was used to investigate the role of serotonin in the locomotor hyperactivity produced by injections of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), muscimol and baclofen into the median raphe nucleus (MR) of unanesthetized rats.
The 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) was microinjected (0.2, 0.5 and 2.0 microg/0.2 microl) in different brain areas of female Wistar rats: median raphe nucleus (MnR); medial septal area (MS); anterior corticomedial amygdaloid nucleus (ACoM); and dorsal periaqueductal gray (DPAG).
In the median raphe nucleus (B8) and the B9 cell group in the medial lemniscus, 8-OH-DPAT induced a marked decrease in labeling 30 min after injection.
We have examined the effects of the systemic administration of the selective 5-HT1A agonist alnespirone (S-20499) on in vivo 5-hydroxytryptamine (5-HT) release in the dorsal raphe nucleus, the median raphe nucleus and four forebrain areas innervated differentially by both (dorsal striatum, frontal cortex, ventral hippocampus and dorsal hippocampus). In contrast, the decrease in 5-HT elicited in the median raphe nucleus was more marked than that in the dorsal raphe nucleus (to ca 30 and 60% of baseline, respectively).
Serotonergic neurons of the median raphe nucleus heavily innervate hippocampal GABAergic interneurons located in stratum radiatum of area CA1, suggesting that this strong subcortical projection may modulate interneuron excitability.
We review evidence showing that the serotonin-containing neurons of the median raphe nucleus desynchronize the hippocampal electroencephalogram, presumably by disrupting the rhythmical discharge of septal cholinergic and GABAergic neurons.
In the presence of a saturating concentration of granisetron (1.0 microM), highest levels of specific [ 125I]R(+)-zacopride, binding sites (defined by R(+)-zacopride, 1.0 microM; R(+)-site), were detected in the olfactory tubercle, thalamus, corpus callosum, colliculus, dorsal and median raphe nucleus, spinal cord and the pons (8.0-13.0 fmol/mg).
In all cases, the PHA-L injections labeled innervating fibers both within the ependyma and in the SCO, whereas injections into the median raphe nucleus or in other raphe nuclei (i.e., the raphe pallidus and the raphe pontis) labeled fibers neither in the SCO nor in the ependyma.
Extracellular 5-HT was measured in the dorsal raphe nucleus (DRN), median raphe nucleus (MRN), nucleus accumbens, hypothalamus, frontal cortex, dorsal and ventral hippocampus.
Recent neurochemical studies of the properties of 5-hydroxytryptamine (5-HT) pathways arising from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) have measured extracellular 5-HT in brain regions with reported preferential DRN or MRN 5-HT inputs.
To examine possible sites of action of 8-OH-DPAT, 8-OH-DPAT (0.5 microg (100 nl) or 1.0 microg (200 nl)) was microinjected into the intergeniculate leaflet, dorsal raphe nuclei, and the median raphe nucleus at circadian time 7.
These results suggest that the median raphe nucleus plays an inhibitory role in the onset mechanism for mounting.
The perfusion of 50 micromol/L citalopram in the dorsal or median raphe nucleus reduced 5-HT(ext) in frontal cortex or dorsal hippocampus to 40 and 65% of baseline, respectively.
The suprachiasmatic nucleus (SCN) is densely innervated by serotonergic fibers originating in the median raphe nucleus (MR).
Infusions of 8-OH-DPAT (100 ng) into the median raphe nucleus improved performance accuracy, independent of delay whilst having no effect on any other response measure.
A moderate amount of [ 3H]nisoxetine binding was also observed in the median raphe nucleus.
Extracellular 5-hydroxytryptamine (5-HT) was determined in dorsal raphe nucleus (DRN), median raphe nucleus (MRN) and nucleus accumbens by use of microdialysis in unanaesthetized rats.
Lesion of median raphe nucleus reduced 5-hydroxytryptophan accumulation in hippocampus and in hypothalamus but not in cerebral blood vessels or striatum.
Maximal and minimal basal 5-HT values (in the presence of 1 microM citalopram) were 45.0 +/- 4.8 fmol/fraction in the median raphe nucleus and 8.4 +/- 0.4 fmol/fraction in the dorsal hippocampus. Maximal reductions (to approximately 25% of predrug values) were observed in cortex and striatum and in median raphe nucleus. Yet the differential reduction of 5-HT release in the median raphe nucleus and hippocampus suggests the presence of complex mechanisms of control of 5-HT release in these neurons..
The median raphe nucleus appears to exert a modulatory influence upon these behaviors, which probably is mediated by serotonergic neural pathways..
In order to examine the effects of alcohol toxicity and thiamine deficiency on serotonergic neurons in the median raphe nucleus (MnR), alcoholic and previously published Wernicke-Korsakoff syndrome (WKS) cases without liver disease, were compared with age-matched non-alcoholic controls.
The dorsal or median raphe nucleus lesions (DRL or MRL, respectively) were made by means of a radiofrequency lesion generator.
The effects of systemic administration of the serotonin (5-hydroxytryptamine) 5-HT1A receptor agonists flesinoxan and 8-hydroxy-2-(di-n-propylamino)tetralin on extracellular 5-HT were measured using microdialysis probes in both median raphe nucleus and dorsal hippocampus.
Comparisons across serotonin cell groups indicated that neurons of the median raphe nucleus, caudal linear nucleus raphe (B8) and the dorsal raphe (B6/B7) expressed the highest levels of GTP cyclohydrolase I mRNA.
Deakin and Graeff have suggested that the pathway connecting the median raphe nucleus (MRN) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress.
Intense MOR1-like immunoreactivity (LI) was seen in the 'patch' areas and subcallosal streak in the striatum, medial habenular nucleus, medial terminal nucleus of the accessory optic tract, interpeduncular nucleus, median raphe nucleus, parabrachial nuclei, locus coeruleus, ambiguous nucleus, nucleus of the solitary tract, and laminae I and II of the medullary and spinal dorsal horns.
The electrophysiological relationship between the hippocampus (HP) and the median raphe nucleus (MRN) was examined in the freely moving rat.
Intense hybridization signals were also observed in the nuclei containing monoaminergic neurons, such as locus coeruleus, the substantia nigra pars compacta, the ventral tegmental area, the dorsal raphe nucleus and the median raphe nucleus.
The present studies use retrograde and anterograde tracing as well as neurotoxic lesion techniques to demonstrate that serotonergic cells in the median raphe nucleus (MR) project to the SCN and that serotonergic cells in the dorsal raphe nucleus (DR) project to the IGL.
During infusion of NMDA (100 and 300 microM) into the median raphe nucleus (MRN), 5-HT was increased by approximately 15 and 80%, respectively.
Extracellular single-unit recording techniques were used to examine the firing characteristics of neurons in the medial septum/diagnol band of Broca complex (MS/DB) following injections of the 5-HT1A agonist, 8-OH-DPAT, into the median raphe nucleus (MRN) of urethane-anesthetized rats.
These structures include: taenia tecta, some fusiform perikarya in the diagonal band of Broca, pyramidal cells in the fifth layer of the cerebral cortex, paraventricular nuclei, zona incerta, medial habenular nuclei, red nuclei, dorsal tegmental nuclei, median raphe nucleus, nuclei pontis, cochlear and vestibular nuclei and some Purkinje cells in the most lateral segment of the cerebellar cortex.
There is strong evidence to suggest that (1) the catalepsy produced by dopamine D1 or D2 receptor antagonists can be completely antagonized by the administration of 5-HT1A receptor agonists acting at 5-HT autoreceptors in the median raphe nucleus; (2) the catalepsy produced by a dopamine D2 receptor antagonist can be completely antagonized by treatment with a 5-HT2A/C receptor agonist; and (3) the catalepsy produced by blockade of either dopamine D1 or D2 receptors is not affected by the administration of a 5-HT2A/C receptor antagonist.
Sound stress increased 5-HTP accumulation in the median raphe nucleus (MRN) twofold over that from sham-stressed controls, but did not change 5-HTP accumulation significantly in dorsal raphe nucleus (DRN) or hindbrain.
Comparison of serotonin-immunoreactive (SER-IR) neurons in nucleus raphe dorsalis (NRD) and median raphe nucleus (MRN) of 25-d-old rat pups exposed to 70 mg/kg/d 2,4-dichloro-phenoxyacetic acid through mothers milk and control pups was made using an immunohistochemical analysis.
Electrical stimulation of either the dorsal or median raphe nucleus evoked a release of 5-hydroxytryptamine in the hippocampus. Whereas stimulation of the dorsal raphe nucleus also released 5-hydroxytryptamine in the frontal cortex, stimulation of the median raphe nucleus did not. No release of 5-hydroxytryptamine was evoked when electrodes were located in regions bordering the dorsal raphe nucleus and the median raphe nucleus. The amounts of hippocampal 5-HT released by stimulation of the dorsal or median raphe nucleus were found to be similarly altered by a 5-hydroxytryptamine uptake inhibitor (citalopram) and calcium-free perfusion medium, and also by increasing stimulation frequency (2-10 Hz). Furthermore, the amount of 5-hydroxytryptamine released by electrical stimulation of either the dorsal raphe nucleus or median raphe nucleus was markedly reduced in rats pretreated with p-chloroamphetamine. In summary, our data show that electrical stimulation of the dorsal or median raphe nucleus releases 5-hydroxytryptamine in a regionally specific manner (hippocampus versus frontal cortex), suggesting that serotonergic nerve terminals of the dorsal and median raphe pathways were being activated selectively. In particular, our data suggest that the neurotoxic action of p-chloroamphetamine may not be targeted solely on serotonergic axons and terminals of the dorsal raphe nucleus but includes those of the median raphe nucleus..
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