This brief review presents a personal perspective on the historical development of the current knowledge about the biologically important concept of functional antagonism between adenosine A2A and dopamine D2 receptors in caudate-putamen, accumbens, and tuberculum olfactorium. 
In mice treated with DDC+MPTP, degenerative areas were found in striatum, substantia nigra and tuberculum olfactorium by assessment of the binding of [ 125I]RTI-121, a DA transporter ligand.
We developed a method to detect the specific enhancer effect of synthetic enhancer substances [ (-)-deprenyl, (-)-PPAP, (-)-BPAP] by measuring the release of transmitters from freshly isolated selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus, raphe) by the aid of HPLC with electrochemical detection. The orienting-searching reflex activity of the rats increased proportionally to the time elapsed from the last feed and the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium, that of norepinephrine released from the locus coeruleus and that of serotonin released from the raphe increased significantly in the hungry rats proportionally to the time of fasting.
Due to their enhancer effect, the amount of catecholamines released from selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus) is significantly higher in rats treated with an enhancer substance than in saline treated rats. Compared to saline treated rats, the enhancer substances significantly increased the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium and the amount of norepinephrine released from the locus coeruleus; alpha-tocopherol was ineffective.
Intense feeding responses associated with an increased duration of feeding behavior were consistently recorded after injections of MK-801 or CNQX into the medial two-thirds of the tuberculum olfactorium (TO), the ventral aspect of lobus parolfactorium (LPOv), or the ventral pallidum (VP).
Unbiased stereological analysis of labelled cells in selected forebrain areas 24 h post BrdU injection showed a significant MeA-training induced increase in labelled cells in both the dorsal VZ surface bordering the intermediate and medial hyperstriatum ventrale (IMHV) and the tuberculum olfactorium (TO).
The neurons projecting to the SN or AVT considerably overlap in the viscerolimbic parts of the striatum, namely the medial and dorsal LPO, nucleus accumbens (Ac), tuberculum olfactorium, bed nucleus of the stria terminalis and ventral paleostriatum.
The amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from locus coeruleus and serotonin from the raphe, was significantly higher in four and five weeks old rats than in three month old ones, proving that the catecholaminergic/serotoninergic activity enhancer (CAE/SAE) regulation works unrestrained during developmental longevity and is restricted thereafter.
The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10(-12) - 10(-14) M (-)BPAP.
The estimations were carried out in the striatum and limbic forebrain containing: nucleus accumbens, septum, limbic cortex, amygdala, tuberculum olfactorium.
AR-ir material was detected in the nucleus of cells located in a variety of brain areas in the preoptic region and the hypothalamus including the medial preoptic (POM), the supraoptic, the paraventricular (PVN), and the ventromedial (VMN) nuclei, but also in the tuberculum olfactorium, the nucleus accumbens/ventral striatum, the nucleus taeniae, the tuberal hypothalamus, the substantia grisea centralis (GCt), and the locus ceruleus.
A high density of binding sites was detected, radioautographically, in several layers of the cerebral cortex, in the hippocampus, dentate gyrus, tuberculum olfactorium, caudate putamen, medium densities in the globus pallidus, thalamus, spinal cord dorsal horn, and motoneurons, whereas the cerebellum, pons, and medulla were, with a few exceptions, e.g., locus coeruleus, poorly labeled.
The present studies indicated that compared to animals from the home cage, those exposed to the high-light aversive unfamiliar test condition, had significantly increased levels of 5-hydroxyindoleacetic acid (5-HIAA), the metabolite of 5-hydroxytryptamine (5-HT), in the tested brain regions including amygdala, entorhinal cortex, frontal cortex, temporal cortex, tuberculum olfactorium, hippocampus, nucleus accumbens, and striatum. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the metabolites of dopamine (DA), were increased in tuberculum olfactorium, nucleus accumbens, and striatum. When compared to the low-light familiar test condition (LF), the levels, following exposure to the highlight unfamiliar situation, of 5-HIAA were significantly increased in the amygdala, entorhinal cortex, tuberculum olfactorium, hippocampus, and nucleus accumbens, while the 5-HIAA levels remained unchanged in the frontal cortex, temporal cortex, and striatum. The DOPAC and HVA levels were also increased by the HU situation in the amygdala, tuberculum olfactorium, and nucleus accumbens.
As an indicator of the basic activity of catecholaminergic neurons, the resting release of dopamine from the striatum, substantia nigra, and tuberculum olfactorium, and of norepinephrine from the locus coeruleus, was measured in 2-, 4-, 8-, 16-, and 32-week-old male and female rats.
There was no difference between HP and LP rats in the amount of dopamine released from the striatum, the substantia nigra and the tuberculum olfactorium.
Marked differences between medial and lateral insulae terminales olfactoriae permit a clear delineation between the human Nucleus accumbens and the lateral, rudimentary tuberculum olfactorium: the basis for modifying the concept of a ventral striatum in man..
Adenosine A2A receptors, studied by [ 3H]CGS 21680 binding and by in situ hybridization, were found to be present in intrinsic neurons in the caudate putamen, nucleus accumbens and tuberculum olfactorium.
The mechanism of the CAE effect of (-)deprenyl and (-)PPAP, a deprenyl-derived substance devoid of MAO inhibitory potency, was studied in rats by measuring: a) the release of catecholamines from striatum, substantia nigra, tuberculum olfactorium and locus coeruleus; b) the stimulation induced release of 3H-noradrenaline from the isolated brain stem; and c) the antagonistic effect against tetrabenazine-induced depression of learning in the shuttle box.
Significantly decreased serotonin levels and increased turnover were found in nucleus caudatus putamen, nucleus accumbens and tuberculum olfactorium of adult rats treated as neonates with serotonin antiserum.
It has previously been shown that caffeine, in a dose-dependent manner, increases the expression of the protooncogene c-fos in the rat brain, predominantly in the caudate-putamen and tuberculum olfactorium.
Dopamine metabolism is enhanced in structures of both nigrostriatal and mesolimbic systems, as revealed by increased metabolites content (that of homovanillic acid in striatum and concentration of 3,4-dihydroxy-phenylacetic acid in nucleus accumbens with tuberculum olfactorium) along with unchanged neurotransmitter levels in qk/qk mice.
We therefore measured the resting release of dopamine from the striatum, substantia nigra and tuberculum olfactorium, and of noradrenaline from the locus coeruleus, as an indicator of the basic activity of catecholaminergic neurons in the brain, in 2,4,8,16 and 32 weeks old male and female rats.
On the 6-OHDA-injected side, DA and metabolites levels were reduced by > 70-90% in the striatum, the nucleus accumbens and the tuberculum olfactorium, while in the mesencephalon a 50% decrease was found. In contrast, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were increased in the ipsilateral striatum (> 180%), and tuberculum olfactorium (> 120%).
Moclobemide had decreased MAO-A activity in all areas examined by a dose-dependent manner; the largest decrease was observed in tuberculum olfactorium and striatum. MAO-A inhibitory properties on tuberculum olfactorium and striatum could be of interest according to some animal models of depression..
Treatment with (-)deprenyl enhanced the release of dopamine from striatum, substantia nigra and tuberculum olfactorium (significant in 0.01-0.25 mg/kg) and the release of noradrenaline from the locus coeruleus (significant in 0.05-0.25 mg/kg), whilst the release of serotonin from the raphe was diminished (significant in 0.05-0.25 mg/kg in males and 0.25 mg/kg in females).
accumbens with tuberculum olfactorium) systems were found to be increased in the aged animals.
Very high levels of [ 3H]YM-09151-2 binding were found in the caudate-putamen, nucleus accumbens, tuberculum olfactorium and the insula of Calleja, to each of which midbrain dopaminergic neurons project densely.
Target neurons were present in ventral periventricular brain regions including tuberculum olfactorium, nucleus accumbens, cortex piriformis, primordium hippocampi, nucleus striae terminalis, dorsal ventricular ridge, amygdala, nucleus infundibularis and tectum opticum.
Local IC microinjection of OXT in physiological doses into the posterior olfactory nucleus, tuberculum olfactorium, nucleus accumbens, central amygdaloid nucleus, and the hippocampus inhibited the development of tolerance to and dependence on morphine as well as cocaine-induced sniffing behavior and tolerance to cocaine.
ir-cGnRH II fibers were prominent in limbic structures (cortex piriformis, lateral to nucleus taeniae, hippocampus); olfactory areas (tuberculum olfactorium, nucleus subhabenularis lateralis, nucleus septalis lateralis); areas that in other avian species have steroid-concentrating cells or receptors (medial edge of lobus parolfactorius, nucleus septalis medialis, nucleus periventricularis magnocellularis, nucleus dorsomedialis posterior thalami); and areas containing ir-GnRH I cells or fibers but not in median eminence.
We investigated the ligand binding properties in vitro of two splice variants of the cloned human dopamine D2 receptor (the 443 and 414 amino acids long forms called D2L and D2S, respectively), expressed in 293 human kidney cells, in comparison with those of the dopamine D2 receptors in rat striatum, nucleus accumbens and tuberculum olfactorium.
They were high in the tuberculum olfactorium, lateral septum, nucleus accumbens, MPOA, PVN, dorsomedial nucleus and regions of the MBH including the arcuate nucleus, tuber cinereum and ventral hypothalamic tract (VHT).
accumbens lateralis and medialis, tuberculum olfactorium) and most of the analyzed planes [ interaural 7.7-10.2 according to the atlas of Paxinos and Watson (35)].
Dopamine efflux following single pulse or train of pulse stimulations was measured in slices of rat caudate putamen, nucleus accumbens and tuberculum olfactorium, using fast cyclic voltammetry at a carbon fibre microelectrode; 1, 5, 10, 20 or 50 pulses were applied at each location at frequencies varying from 10 Hz to 500 Hz. The tuberculum olfactorium releases the least dopamine of the three regions following a single pulse stimulation (approximately 40 nM dopamine), but the ratio of peak dopamine release following trains of 20 pulses (50 Hz) when compared to single pulse can result in a value approaching 20.
In mice of eight inbred strains--BALB/c, AKR/J, DBA/2, CBA, C57B1/6, DD, CC57Br, and C3H/He--brain dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in striatum and nucleus accumbens with tuberculum olfactorium, the structures of two main dopaminergic systems--nigrostriatal and mesolimbic--were determined.
After daily haloperidol (5 mg/kg, IP, for 6 days) or haloperidol decanoate (70 mg/kg, IM, given once or twice) treatment, immunoreactive neurons appeared diffusely in the whole CP and in the core part of the nucleus accumbens (Acb) and less frequently in the outer shell part of the Acb and the cell-dense layer of the tuberculum olfactorium (TuO).
The in vitro binding affinity of ocaperidone, risperidone, and haloperidol for D2 receptors was exactly the same when measured in membranes from rat striatum, nucleus accumbens, tuberculum olfactorium, and human kidney cells expressing the cloned human D2 receptor (long form). In the tuberculum olfactorium, 5HT2 and D2 receptors were also distinguished with risperidone. Ocaperidone, risperidone, and haloperidol readily increased the levels of the dopamine metabolites 3,4-dihydroxybenzene acetic acid and homovanillic acid in the striatum, the nucleus accumbens, the tuberculum olfactorium, and, to some extent, the frontal cortex.
Behavioural and neurochemical effects of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in mice have been studied in order to determine the change in the neurotransmitter profile of the following areas of the brain: substantia nigra (SN), nucleus caudatus putamen (NCP), limbic system (LS; tuberculum olfactorium and nucleus accumbens), medulla oblongata (MO) and cerebellum (CER).
Dopamine (DA) is a neurotransmitter which modulates the transfer of information along fast-conducting pathways at the level of two main nodal points: the ventral striatum, composed by limbic areas (nucleus accumbens, tuberculum olfactorium) and the dorsal striatum, composed by extrapyramidal nuclei (caudate-putamen).
Treatment with SCH 23390, SCH 39166, A-69024 or SKF 38393 failed to alter D1 receptor binding in the posterior caudatus-putamen and the tuberculum olfactorium.
In the present experiments, dopaminergic systems of Sprague-Dawley rats were lesioned by 6-OHDA infused into either the tuberculum olfactorium or nucleus accumbens, two of the structures implicated in drug-related reinforcement. accumbens or tuberculum olfactorium, preference for ethanol increased significantly with absolute intakes exceeding 4.0 g/kg at the 7% concentration during the first postlesion drinking test. accumbens and tuberculum olfactorium is to regulate the craving for a drug with addictive liability such as ethanol.
Fibers and terminals were observed in the area corticoidea dorsolateralis, area parahippocampalis, hippocampus, hyperstriatum accessorium, hyperstriatum dorsale, archistriatum, tuberculum olfactorium, nuclei dorsolateralis and dorsomedialis of the thalamus, and throughout the hypothalamus and the median eminence. A striking mismatch occurred in the hyperstriatum ventrale, neostriatum, tectum opticum (high to moderate density of binding sites but only few immunoreactive profiles), and in the tuberculum olfactorium, median eminence, and spinal cord (lower density of binding sites but abundant immunoreactive profiles).
In vivo acute intermittent injections of nicotine decrease GABA utilization in the hypothalamus and glutamate levels within the nucleus caudatus and the subcortical limbic forebrain (mainly tuberculum olfactorium and nucleus accumbens).
In addition to his topographic description it was possible to define the tuberculum olfactorium and several subdivisions of the interstitial nucleus of the stria terminalis.
High or very high densities of binding sites were found in the hyperstriatum, tuberculum olfactorium, hypothalamic nuclei, tectum opticum and some medullary nuclei.
Intraventricular injections of neurotensin (0.03-3 nmol, 30 min) reduced dose-dependently specific [ 3H]NPA binding (0.25 nM) in the caudate-putamen (-38 +/- 4%), nucleus accumbens (-42 +/- 5%), tuberculum olfactorium (-52 +/- 7%) and in the intermediate lobe of the pituitary gland (-17 +/- 2%). It was not possible to demonstrate coexistence in the caudate-putamen, nucleus accumbens, tuberculum olfactorium and median eminence, in view of the high density of dopamine nerve terminals present in relation to the few visualized neurotensin terminals.
In Xenopus, AchE staining of fibers and terminals is restricted to the subpallium (medial septum, tuberculum olfactorium, striatum, nucleus accumbens, and medial amygdala); cell bodies are AchE positive in parts of the subpallium and rostral pallium.
Dopamine content was higher in the tuberculum olfactorium of domesticated animals, being lower in the striatum and n.
The results demonstrated that partial di-mesencephalic hemitransections produced a marked reduction of DA fluorescence (quantitative histofluorimetry) on the lesioned side in the nucleus caudatus putamen, anterior nucleus accumbens and posterior lateral tuberculum olfactorium. On the hemitransected side chronic nicotine treatment increased DA stores in the DA nerve terminals of the nucleus caudatus putamen and the posterior lateral tuberculum olfactorium.
Caerulein decreased GABA levels in the nucleus accumbens, tuberculum olfactorium and substantia nigra and diminished GABA turnover rates in the striatum, nucleus accumbens and substantia nigra, as estimated from the rate of GABA accumulation after inhibition of GABA transaminase by aminooxyacetic acid (AOAA).
Somata positive for ChAT were observed in the striatum, nucleus accumbens, the dorsal ventricular ridge, nucleus olfactorius anterior, tuberculum olfactorium, diagonal band of Broca, septum, bed nucleus of the medial forebrain bundle and lateral preoptic area.
The TH-IR terminal density was reduced by 92% in striatum, 77% in nucleus accumbens and by 72% in tuberculum olfactorium.
It is suggested that the vessel represents a persistent anastomosis between the anterior and middle cerebral arteries over the tuberculum olfactorium, the anastomosis being a predecessor of the recurrent artery of Heubner in phylogenetic development.
5-HT content of the tuberculum olfactorium and basal ganglia was found to be increased significantly at a time when 5-hydroxyindoleacetic acid (5-HIAA) content showed a decrease. The alterations in the levels of the indoleamine in tuberculum olfactorium and its relationship with dosage as well as duration and intensity of LON-954 tremor indicate the involvement of the mesolimbic system in its action.
As judged using haloperidol, [ 3H]spiperone identified dopamine receptors in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus, but not in frontal cortex or nucleus accumbens. The substituted benzamide compounds alizapride, metoclopramide, clebopride and YM 09151-2 prevented the accumulation of [ 3H]spiperone in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus. The (-)-isomers of both drugs prevented the accumulation of [ 3H]spiperone in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus.
The levels of homovanillic acid (HVA) in the striatum and tuberculum olfactorium, 5-hydroxyindolacetic acid (5-HIAA) in the cerebellum and 3-methoxy-4-hydroxypheniglycol (MHPG) in the frontal cortex were determined.
Gi3-alpha-peptide staining was observed in perikarya in the hippocampus and in fibers in the nucleus accumbens, tuberculum olfactorium, bed nucleus of stria terminalis, and a spino-thalamic tract, where it coexisted with CCK-like immunoreactivity as well.
The in-vivo administration of [ 3H]spiperone caused an accumulation of radioactivity in the substantia nigra, tuberculum olfactorium, nucleus accumbens, striatum and frontal cortex when compared with cerebellar levels. Haloperidol (0.01-1.0 mg kg-1 i.p.) dose-dependently prevented the accumulation of [ 3H]spiperone in the substantia nigra, tuberculum olfactorium, striatum and nucleus accumbens. The effects of sulpiride on other areas were not consistent; there was a suggestion of a reduction in the accumulation of [ 3H]spiperone in tuberculum olfactorium and striatum, but not in nucleus accumbens. The functional effect produced by haloperidol correlated with its ability to define [ 3H]spiperone binding in-vivo to dopamine receptors in the substantia nigra, striatum and tuberculum olfactorium.
With the [ 3H]ACh and [ 3H]Nic radioligands, a strong labelling was observed in various thalamic nuclei, including the medial habenula, a moderate labelling in different areas of the cortex cerebri, the nucleus caudatus putamen, the nucleus accumbens and tuberculum olfactorium and a uniform weak labelling in the hypothalamus.
Special attention was focused on CCK-LI in mesencephalic dopamine neurons and in their projection areas including nucleus accumbens, tuberculum olfactorium and particularly the caudate nucleus.
Chronic SCH 23390 treatment increased D-1 receptor density by 30 to 40% in the striatum, accumbens and tuberculum olfactorium; receptor affinity remained unchanged. Haloperidol had no effect on D-1 receptor Bmax or Kd values, although, when administered with SCH 23390, reduced the D-1 receptor upregulation induced by the D-1 antagonist in striatum and tuberculum olfactorium, but not in nucleus accumbens. These results may be attributable to D-1/D-2 dopamine receptor interactions occurring in the striatum and tuberculum olfactorium and may have implications for the prevention and treatment of drug-induced extrapyramidal disorders..
The time course for recovery of binding of the D1 dopamine receptor antagonist radioligand [ 3H]SCH 23390, after administration of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), was studied in the neostriatum, nucleus accumbens, tuberculum olfactorium and claustrum of the rat by means of quantitative receptor autoradiography.
The intraperitoneal administration of L-dopa and a series of ester prodrugs of L-dopa to reserpinized mice produced elevations of striatal and tuberculum olfactorium homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. Only the phenoxyethyl ester caused elevations of both striatal and tuberculum olfactorium HVA and DOPAC, greater than those measured following L-dopa administration. Overall the m-trifluoromethylbenzyl, phenylethyl, p-chlorophenylethyl and p-methoxyphenylethyl ester prodrugs produced greater elevations of striatal and tuberculum olfactorium HVA, but not DOPAC, compared with L-dopa. The administration of the 2-tetrahydropyranyl-methyl derivative only enhanced striatal HVA and striatal and tuberculum olfactorium DOPAC concentrations. The alterations in striatal and tuberculum olfactorium HVA and DOPAC levels observed did not correlate with the ability of these compounds to elicit locomotor activity in reserpinized mice..
The only exception to this seems to be the MPTP-induced chronic decrease of DA in the nucleus accumbens and the tuberculum olfactorium where no morphologic changes have been found so far..
We have identified MD afferents from the following structures: area septalis, amygdaloid complex, hypothalamus, mamillary bodies, tuberculum olfactorium, claustrum, ventral tegmental area, zona incerta, substantia nigra, griseum centralis, formatio reticularis mesencephali and pontis oralis.
A minor mesostriatal projection is overshadowed by the large mesolimbic projection to the accumbens, tuberculum olfactorium, septum lateralis and n.
The effect of dopamine D-2 receptor activation on dopamine D-1 stimulated cyclic AMP accumulation was investigated in slices of rat striatum and limbic forebrain (nucleus accumbens and tuberculum olfactorium).
The highest density of [ 3H]terguride binding sites was found in the striatum and tuberculum olfactorium.
In cysteamine-treated rats a marked decrease in SOM-28(15-28)-like immunoreactivity (1.1) could be recorded subjectively at all antibody concentrations in fibers in several brain areas, including nucleus accumbens, tuberculum olfactorium and the hypothalamic ventromedial and arcuate nuclei.
The in vivo administration of [ 3H]-spiperone to rats leads to a selective accumulation of radioactivity in the olfactory lobes, tuberculum olfactorium, nucleus accumbens, striatum, substantia nigra, hippocampus, frontal cortex and hypothalamus, when compared to the cerebellum. [ 3H]-spiperone in vivo mainly labels dopamine receptors in striatum, tuberculum olfactorium, hypothalamus, substantia nigra and olfactory lobes.
A single injection of caerulein (400 micrograms/kg, i.p.) significantly elevated 5-hydroxyindoleacetic acid (5HIAA) levels in the prefrontal cortex lateral field, nucleus accumbens, tuberculum olfactorium and striatum after 2 hours, together with a significant increase in striatal serotonin (5HT).
[ 3H]GBR 12783 bound in a sodium-dependent manner to membranes prepared from striatum, nucleus accumbens and tuberculum olfactorium.
Other discrete areas of the CNS are enriched with somatostatin receptors: locus coeruleus, tuberal nuclei of the hypothalamus, claustum, tuberculum olfactorium as well as spinal trigeminal nucleus and substantia gelatinosa of the spinal cord.
By means of quantitative receptor autoradiography in combination with inactivation of dopamine (DA) receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), it was demonstrated in the male rat that [ 3H]spiperone predominantly labels D2 receptors in the striatum, nucleus accumbens and tuberculum olfactorium, and predominantly non-DA receptors in the frontoparietal cortex, probably mainly serotonin type 2 (5-HT2) receptors in layer IV.
Dopamine (DA) levels and utilization in the telencephalon were measured by quantitative histofluorimetry in discrete DA nerve terminal systems of the neostriatum, nucleus accumbens and tuberculum olfactorium. Exposure to unfiltered but not to filtered (Cambridge glass fibre filter) cigarette smoke resulted in a dose-dependent increase in DA utilization in the diffuse types of DA nerve terminal systems in the anterior nucleus accumbens and the lateral posterior tuberculum olfactorium. The DA utilization in various parts of the neostriatum and in the dotted type of DA nerve terminals in the medial posterior tuberculum olfactorium were unaffected by acute intermittent exposure to cigarette smoke. The DA levels in the various DA nerve terminal systems in neostriatum, nucleus accumbens and tuberculum olfactorium were unaffected with the exception of the dotted and CCK positive type of DA nerve terminals of the nucleus accumbens, where a small reduction of the DA stores was shown following acute intermittent exposure to smoke from 4 cigarettes. It is suggested that the nicotine component of the cigarette smoke via activation of nicotinic cholinergic receptors can enhance DA release in discrete DA nerve terminal systems of the nucleus accumbens and tuberculum olfactorium.
From within the telencephalon the nucleus basalis prosencephali also receives fibres from the tuberculum olfactorium and the peri-ectostriatal belt, suggestive of olfactory and visual input.
The injection of tetralin into the substantia nigra also caused biochemical changes in limbic areas (nucleus accumbens and tuberculum olfactorium), where the levels of dopamine and DOPAC were elevated, and in the frontal cortex where the levels of DOPAC were reduced.
Other sites of immunoreactivity in the central nervous system are the region of the substantia gelatinosa of the spinal cord, fibres in Lissauer's tract, the tractus solitarius and the tuberculum olfactorium.
Further, whilst ICV MPP+ alone failed to influence the biochemistry of the limbic areas (nucleus accumbens plus tuberculum olfactorium), in the presence of deprenyl MPP+ caused 20-40% reductions in levels of limbic NA, DA, DOPAC, HVA, 5-HT and 5-HIAA.
This action of chronic treatment of T3 or T4 was highly selective and no changes in DA levels could be demonstrated in any DA nerve terminals analyzed in the nucleus caudatus putamen; nucleus accumbens and tuberculum olfactorium.
The in vivo accumulation of 3H-N-propyl norapomorphine in mouse striatum and tuberculum olfactorium and its inhibition by a series of classical neuroleptics and discriminant benzamide derivatives previously identified in behavioural and radioligand experiments has been studied.
The two most significant actions of CCK-58 are a marked lowering of TSH secretion and a selective increase of DA turnover in DA-CCK co-existing synapses in the nucleus accumbens and tuberculum olfactorium..
No significant change in DA metabolites was found in the other 7 areas (polar and medial fields of prefrontal cortex, anterior cingulate cortex, nucleus accumbens, tuberculum olfactorium, septum and amygdala).
The greatest concentration of the sites occurs in frontal cortical tissue, but they were also detected in striatum, nucleus accumbens and tuberculum olfactorium as well as on membranes of cat and human platelets.
Taking the levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as a measure of the rate of DA turnover, it was found that prazosin and phenoxybenzamine decreased, whereas piperoxane and yohimbine increased the turnover rate both in the corpus striatum and in the tuberculum olfactorium.
Within the ventrolateral telencephalon, the nucleus accumbens, nucleus of the diagonal band, and tuberculum olfactorium contained enkephalinergic cell bodies and fibers while only enkephalinergic fibers were observed in the portion of the avian telencephalon that has been termed the ventral paleostriatum (Kitt and Brauth, '81; Reiner et al., '83).
Injections of tetralin (0.1 micrograms) not only into the nucleus accumbens but also into the tuberculum olfactorium, septal nucleus, anterior olfactory nucleus, anteromedial fibre system, claustrum and caudate-putamen could effect inhibition of motor activity.
The increase of DA was less pronounced in the tuberculum olfactorium and there was no change in the frontal cortex.
The rate of removal of 3,4-dihydroxyphenylacetic acid (DOPAC) in nine rat brain areas (striatum, nucleus accumbens, tuberculum olfactorium, hypothalamus, lateral hippocampus, occipital cortex, brain stem, cerebellum, and retina) was calculated from its exponential decline after monoamine oxidase inhibition by pargyline. In saline- as well as in haloperidol-pretreated rats it was found that the total catecholamine synthesis rate in the typical dopaminergic areas (striatum, nucleus accumbens, and tuberculum olfactorium) was of the same order of magnitude as the DOPAC rate of removal.
Cortical hydroxytryptamine (5-HT) and noradrenaline concentrations as well as hypothalamic 5-HT, were significantly elevated by tranylcypromine, as was dopamine in the striatum, nucleus accumbens and tuberculum olfactorium.
Topographically organized dopaminergic projections from the extrapyramidal structures of the ventral mesencephalon (substantia nigra and ventral tegmental area) to the dorsal (body of caudate-putamen) and ventral (anterior-ventral caudate, nucleus accumbens, tuberculum olfactorium) striatum subserve sensorimotor integration in the rat.
It was discovered that the DA neurons innervating the striatum and nucleus accumbens underwent degeneration in the aging brain both at the pre- and post-synaptic level, while the DA synapses within the tuberculum olfactorium remained intact.
The intra-accumbens effectiveness of the dopamine agonists could not be mimicked by injections above the nucleus accumbens (into the head of the caudate-putamen complex) or below the nucleus accumbens (into the tuberculum olfactorium) (with the exception of the effectiveness of bromocriptine administered into the tuberculum olfactorium).
By means of the dopamine (DA) agonist radio ligand 3H-N-propylnorapomorphine (3H-NPA) the effects of cholecystokinin-8 (CCK-8) have been evaluated in vitro on the binding characteristics of the DA agonist sites in membrane preparations from the subcortical limbic forebrain containing mainly nucleus accumbens and tuberculum olfactorium.
The changes were restricted to the pyriform cortex, amygdala, hippocampus (most pronounced in the CA1 sector), gyrus olfactorius lateralis, bulbus olfactorius and tuberculum olfactorium.
The habenular complex, nuclei anterioventralis and medialis thalami, nucleus caudatus putamen, amygdaloideus lateralis, septal nuclei, nucleus nervi hypoglossi, nucleus reticularis lateralis, tuberculum olfactorium, nucleus tractus diagonalis brocae, stratum pyramidale hippocampi, nucleus paraventricularis thalami, nucleus dorsalis nervi vagi, nucleus tractus spinalis nervi trigemini and nucleus reticularis thalami show an increase in the enzyme activity.
Evidence presented suggests that the earliest fibers within the primordial septum are related to the tuberculum olfactorium and the medial forebrain bundle, that septohippocampal fibers appear at 10 weeks, hippocamposeptal fibers by 11.5 weeks, and that, later, stria terminalis fibers develop.
In saline-treated control animals and in hypophysectomized rats 1 week or 1 month following surgery, administration of sulpiride caused marked elevations of striatal, nucleus accumbens and tuberculum olfactorium, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations which were maximal 4-8 h following drug administration. The maximal increases in nucleus accumbens and tuberculum olfactorium were generally comparable in control and hypophysectomized animals, except for a greater increase in HVA levels in the nucleus accumbens 1 month following hypophysectomy.
The effect of the metabolically stable enkephalin pentapeptide analog, D-Ala2-D-Pro5-enkephalinamide monoacetate (DAP) (WY 42, 186) was studied on amphetamine-induced hyperactive behavior and on dopamine release from tuberculum olfactorium in male, Sprague-Dawley rats. In vivo electrochemical evidence, derived from catecholamine sensitive electrodes, showed that the D-Ala2-D-Pro5-enkephalinamide monoacetate did not significantly alter dopamine release from the tuberculum olfactorium, a mesolimbic terminal brain region.
Forty-five minutes after fencamfamine (10 mg/kg), the levels of homovanillic acid in the tuberculum olfactorium, nucleus accumbens and striatum, and those of dihydroxyphenylacétic acid in accumbens were increased. Dihydroxyphenylacétic levels in tuberculum olfactorium and striatum were not changed. Forty-five minutes after amphetamine (5 mg/kg) the levels of homovanillic acid in tuberculum olfactorium, accumbens and striatum, and those of dihydroxyphenylacétic in accumbens were not changed; dihydroxyphenilacétic levels in tuberculum olfactorium and striatum were decreased.
Less neurons projecting to the hippocampal cortex were observed in the ventromedial part of basal telencephalon (tuberculum olfactorium, n.
From these curves the rate of formation of DA and the rate of removal of DOPAC were calculated, within one experiment, for the striatum, tuberculum olfactorium and frontal cortex.
Bilateral electrolesions of the caudate-putamen, nucleus accumbens or tuberculum olfactorium attenuated spontaneous climbing for the first 5-9 postoperative days, the accumbens lesions being most effective.
injection 125J-LVP or its large fragments appeared in the hypothalamus, hippocampus, tuberculum olfactorium and brain stem. LVP produced an increase of noradrenaline level in the hypothalamus, hippocampus and tuberculum olfactorium.
Both the frontal cortex and the entorhinal and perirhinal cortices appear to project also to the nucleus caudatus and the tuberculum olfactorium. The projection from the hippocampus was found to extend also to the tuberculum olfactorium.
The effect of GABA on acetylcholine (ACh) release was investigated on superfused slices of guinea-pig cerebral cortex (CC), caudate nucleus (CN), tuberculum olfactorium and brain stem.
The immunoreactive perikarya were scattered in the following regions: nucleus tractus diagonalis, medial septum, medial preoptic area, lateral septum, lateral preoptic area, tuberculum olfactorium, suprachiasmatic area, supraoptic area, pericommisural area, anterior commissure, vascular organ of the lamina terminalis (OVLT), lateral hypothalamic region and lateral tuberal region.
accumbens, and the tuberculum olfactorium.
The tuberculum olfactorium of the adult rat was investigated by means of neurohistological, fluorescence histochemical and enzyme histochemical methods. After DFP intoxication, only a small proportion of the neuron population of the tuberculum olfactorium does exhibit an AChE activity; the AChE containing neurons are different as to their size and shape.
accumbens and tuberculum olfactorium, and following a dose of 10 microgram/rat increases of dopamine turnover were observed in the medial part of the nuc.
An increase in the [ 3H]spiroperidol binding in the striatum, tuberculum olfactorium and frontal cortex but not in the cerebellum was detected at all ages in SHR. The DOPA accumulation after injection of the DOPA decarboxylase inhibitor NSD 1015 was greater in the tuberculum olfactorium from 7-week-old SHR. An increase in [ 3H]spiroperidol binding sites was also observed in the striatum and tuberculum olfactorium after 7 weeks of DOCA-salt treatment.
Acute administration of five neuroleptics to rats produced a dose-dependent increase in brain homovanillic acid (HVA) which was of greater magnitude and of longer duration in the corpus striatum than in the tuberculum olfactorium.
0.25-2 micrograms intra-accumbens 6-OHDA caused dose-related decreases in the dopamine content of mesolimbic areas (nucleus accumbens and tuberculum olfactorium) without causing significant changes in mesolimbic noradrenaline or striatal dopamine.
The effects of morphine and oxotremorine on concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the rat striatum and tuberculum olfactorium (TO) have been compared with the effects of the antipsychotic drugs haloperidol, chlorpromazine and clozapine.
A two-compartment model was used to calculate the turnover of acetylcholine in the tuberculum olfactorium and the Nucleus accumbens septi.
The studied structures are termed as follows: main and accessory olfactory bulbs, medial cortex (M 1 and M 2), dorsal cortex (D 1, D 2 and D 3), lateral cortex (L), Septum, tuberculum olfactorium, dorsal and ventral striatum, amygdala and nucleus sphaericus.
No changes in DA turnover are found in the DA cell body groups A9 and A10 or in various DA terminals of forebrain, with a possible exception for the diffuse type of DA terminals in the tuberculum olfactorium where a reduction of DA turnover rate is observed.
Chronic treatment with l-sulpiride (20 mg/kg, twice daily) and haloperidol (0.2 mg/kg, twice daily) for 2 weeks produced behavioral signs of DA receptor supersensitivity in both the striatum and the nucleus accumbens-tuberculum olfactorium region.
[ 3H] Spiroperidol binding is decreased in various dopaminergic brain areas, particularly in striatum and tuberculum olfactorium.
This treatment also produced persistent increases of DA turnover in the tuberculum olfactorium but not in striatum..
The steady-state DA levels of heterogenously innervated areas such as the tuberculum olfactorium determined by quantitative microfluorimetry can be made comparable to the steady-state levels of DA obtained by biochemistry in the entire tuberculum olfactorium by means of a conversion factor which considers the dilution of the DA-containing structures by non-DA-containing nerve cells in the biochemical analysis. the tuberculum olfactorium).
The effect of dopamine (DA) and apomorphine (Apo) on acetylcholine (ACh) release from guinea-pig brain was investigated (i) in superfused slices of cerebral cortex, caudate nucleus, tuberculum olfactorium, brain stem and (ii) in unrestrained, unanaesthetized animals, provided with epidural parietal cups.
Lesions of the tuberculum olfactorium were without effect on spontaneous or amphetamine induced responses.
Septal (n.medialis + lateralis, and n.accumbens) and tuberculum olfactorium lesions enhance the non-associative component (D); accumbens lesions, in addition, impair operation of the C factor.
20 microgram TRH injected bilaterally into the caudate-putamen, tuberculum olfactorium, nucleus accumbens, amygdala, lateral ventricles, midbrain or cerebral cortex failed to induce any increase in locomotor activity (measured using photocells), although other behavioural changes were observed after each injection, and included body shakes, limb tremor, repetitive head and limb movements, biting, scratching and an alert appearance.
In the unanesthetized rat, dopaminergic stores were labeled by 14C-dopamine (1.0 microCi) microinjected in a volume of 1.0 microliters into the caudate nucleus, tuberculum olfactorium, nucleus accumbens or other contiguous sites within the ventral forebrain.
Levels of clozapine in rat striatum and tuberculum olfactorium were quantitated by a gas chromatographic technique.
The neurotoxin 5,7-dihydroxytryptamine was used to selectively deplete 5-HT in the striatum, nucleus accumbens septi, tuberculum olfactorium or substantia nigra. Localised depletion of 5-HT within the nucleus accumbens septi and substantia nigra reduced the cataleptic effects of the neuroleptic agent fluphenazine, while lesions of the striatum or tuberculum olfactorium were without effect.
Conversely, in samples of perfusate obtained from 14C-labeled sites within inferofrontal cortex, periform cortex, diagonal band of Broca, lateral-posterior caudate nucleus, tuberculum olfactorium, lateral olfactory tract or the olfactory nuclear complex, the proportion of DA metabolites remained stable.
The highest level of halopemide is found in septal and thalamic areas whereas the neuroleptics are concentrated in the caudate nucleus, the nucleus accumbens and the tuberculum olfactorium.
Repeated treatment (7 days) with the dipivaloyl ester of apomorphine also attenuated the decrease in NVA levels seen with acute treatment in nucleus accumbens and tuberculum olfactorium; however, the threshold dose inducing tolerance in limbic regions was higher than in striatum.
Lesions of the posterior cortex, the tuberculum olfactorium, and the nucleus accumbens had no effect on self-administration behavior.
The drug selectively reduced DA turnover in the subcortical limbic regions (tuberculum olfactorium and nucleus accumbens) and in the DA terminal islands of the nucleus caudatus in doses of 1-5 mg/kg, whereas the large diffuse DA terminal systems of the nucleus caudatus were unaffected. (3) Studies on uptake of tritiated DA in the nucleus caudatus and tuberculum olfactorium reveal a weak inhibition of DA uptake and retention only in high concentrations (10(-5)-10(-6) M). (5) Studies on the effect of MPME on DA sensitive adenylate cyclase in the nucleus caudatus and the subcortical limbic system (mainly tuberculum olfactorium and nucleus accumbens) suggested that MPME is a partial DA receptor agonist with different intrinsic activity on the DA receptors of the subcortical limbic system and of the nucleus caudatus, the effects in the subcortical limbic system being considerably larger than in the nucleus caudatus.
Repeated treatment with haloperidol and sulpiride induced tolerance to the increases in homovanillic and dihydroxyphenyl acetic acids in the striatum, nucleus accumbens, tuberculum olfactorium and frontal cortex of the rat.
The nucleus accumbens septi and tuberculum olfactorium (NAS-TO), which from part of the mesolimbic dopaminergic system, and the striatum, which is part of the nigrostriatal dopamingeric system, contain high levels of both dopamine (DA) and acetylcholine and resemble each other in some other biochemical properties.
Adenosine caused a dose-dependent stimulation of adenylate cyclase in homogenates from rat striatum and tuberculum olfactorium (200 and 300% stimulation by 100 muM adenosine).
Changes in dopamine metabolite levels in the rat striatum and tuberculum olfactorium, following the administration of three non-antipsychotic butyrophenones (AL-499, AHR-1900 and U-25,927) and a non-antipsychotic benzazepine (SCH-12,679), were compared to the effects seen following the antipsychotics haloperidol, chlorpromazine and clozapine. It is concluded that the dose-dependent elevation of DOPAC in the striatum and tuberculum olfactorium of the rat is a good predictor of antipsychotic efficacy..
The effect of haloperidol, chlorpromazine, thioridazine and sulpride on the levels of DOPAC and HVA, as an index of DA turnover, and on the activity of DA-stimulated adenylate cyclase was investigated inthe striatum, the nucleus accumbens and the tuberculum olfactorium of the rat brain.
3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in the corpus striatum, nucleus accumbens and tuberculum olfactorium of the rat brain, 4 antidepressants, 4 anesthetics, dipropylacetate, ethosuximide and metoclopramide induced a rise of DOPAC and HVA levels in the 3 brain regions.
Changes in stereotyped sniffing, biting and hyperactivity induced by apomorphine and D-amphetamine in the rat were determined after bilateral 6-hydroxy-dopamine (6-OHDA) lesions (8-16 micron/4micron6) of the extrapyramidal caudate-putamen (CP) (anterior and centre), globus pallidus (GP) and substantia nigra (SN), the mesolimbic nucleus (ACB), tuberculum olfactorium (TUO) and central amygdaloid nucleus (ACE).
The extremely dense TH innervations patterns of the caudate nucleus, nucleus accumbens, tuberculum olfactorium and the less dense basket-like innervation of the lateral septal nuclei could also be demonstrated.
A model for the prediction of antipsychotic efficacy based on the dose-dependent increase in levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum and tuberculum olfactorium of the rat is presented. Dopamine, assayed in the striatum and tuberculum olfactorium by a new gas chromatographic procedure was not altered by perlapine. The time--action curves for perlapine and clozapine were virtually identical both in the striatum and in the tuberculum olfactorium.
Of the dopamine-containing areas studied, the elevation of HVA was significantly greater in the frontal cortex than in the striatum, the tuberculum olfactorium or the parietal cortex.
Dopamine injected directly into the caudate--putamen, nucleus accumbens or tuberculum olfactorium of rat brain, following a nialamide pretreatment, caused dose-dependent hyperactivity. The hyperactivity was more intense after injections into the nucleus accumbens, but was limited by the development of stereotyped biting when larger doses of dopamine were injected into the caudate--putamen or tuberculum olfactorium. Pimozide appeared equieffective against the 3 hyperactivity mediated from the mesolimbic areas, the nucleus accumbens and tuberculum olfactorium. Sulpiride, clozapine and thioridazine also caused dose-dependent reductions in the hyperactivity induced by dopamine injections into the caudata--putamen, nucleus accumbens and tuberculum olfactorium, although the doses required to effect this inhibition were notably larger than for the typical neuroleptics. However, the responses to dopamine from the caudate-putamen and tuberculum olfactorium were both antagonised by metoclopramide, the striatal response being the least sensitive. The alpha- and beta-adrenergic blocking agents, aceperone and propranolol, failed to reduce the hyperactivity induced by dopamine injections into the caudate-putamen, nucleus accumbens or tuberculum olfactorium. The abilities of the agents tested to antagonise a hyperactivity induced by dopamine in the striatum or in the mesolimbic areas, the nucleus accumbens and tuberculum olfactorium, are compared with the potential of these agents to induce extrapyramidal side effects and to exert an antipsychotic action in man..
Projections to nucleus accumbens, tuberculum olfactorium, stria terminalis, and cortex frontalis were observed only after 6-OHDA lesion of the A10 cell group.
These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex.
accumbens, while hypothalamus, substantia nigra, substantia grisea pericentralis, tuberculum olfactorium, raphe nuclei and nucleus interpeduncolaris showed lower levels of labelling.
Locomotor stimulation was also found following bilateral administration of dopamine, d-amphetamine and apomorphine into the tuberculum olfactorium, whereas noradrenaline, serotonin and ET 495 produced no, or rather depressant effects.
The mechanisms underlying the dissociation of the extrapyramidal and antipsychotic properties of haloperidol as compared to clozapine were explored by studying the effects of these drugs on dopamine metabolism in the straitum and tuberculum olfactorium (TO) of the rat.
Bilateral electrolytic lesions placed in the extrapyrimidal (caudate-putamen, globus pallidus, substantia nigra), mesolimbic (nucleus accumbens septi, tuberculum olfactorium, nucleus interstitialis stria terminalis, nucleus amygdaloideus centralis) nuclei or the neuronal pathways supplying them showed D145 and amantadine to act in both areas although their action on the extrapyrimidal system was most marked.
The intracerebral injection technique was used to apply dopamine directly into dopamine-containing areas of the mesolimbic system, the nucleus accumbens septi, tuberculum olfactorium and nucleus amygdaloideus centralis. 200 mug dopamine injected bilaterally into the nucleus accumbens septi caused a stereotyped sniffing behaviour and hyperactivity but only a periodic hyperactivity developed after similar injections into the tuberculum olfactorium and no change in behaviour was observed following injections into the nucleus amygdaloideus centralis. After pretreatment with nialamide, the effects of intracerebral dopamine were enhanced, doses of 1-50 mug dopamine causing consistent stereotyped sniffing and a dose-dependent hyperactivity on injection into the nucleus accumbens septi or tuberculum olfactorium. In addition, 50-100 mug dopamine injected into the tuberculum olfactorium caused a periodic biting behaviour.
Several "minor" areas of estrogen accumulation include the tuberculum olfactorium, insulae Calleja, n.
During stimulation of phylogenetically ancient parts of the hypothalamus (the anterior and lateral), neuronal reactions have been recorded in the prepyriform lobe and tuberculum olfactorium.
The two components of stereotypy were differentiated both pharmacologically (using amantadine, reserpine plus alpha-methyl-p-tyrosine and haloperidol) and by lesions placed in areas of the extrapyramidal (caudate--putamen, globus pallidus, substantia nigra) and mesolimbic (nucleus accumbens septi, tuberculum olfactorium, nucleus amygdaloideus centralis) systems. The two stereotypic components were differentially induced by intracerebral injections of apomorphine and (minus)-NPA into the caudate--putamen, nucleus accumbens septi and tuberculum olfactorium. The degree of involvement of the different areas was shown to differ for apomorphine and (minus)-NPA, in particular the nucleus accumbens septi appeared more important for the action of (minus)-NPA and the tuberculum olfactorium for apomorphine.
Included in this were, however, size increase of the structures bulbus olfactorius and tuberculum olfactorium as well as size decrease to a different degree of the other olfactory centers.
Ventrally, the medial and the lateral zones and the medial island constitute the tuberculum olfactorium.
Direct stereotactic injection within the dopaminergic mesolimbic system, and particularly the tuberculum olfactorium, produced constant intense responses.
The occurrence of the major dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the tuberculum olfactorium of the rat was demonstrated by gas chromatography. The ratio of DOPAC to HVA in the tuberculum olfactorium was greater than the ratio of these metabolites in the striatum. The effect of pargyline and probenecid on dopamine metabolite levels was similar for both the tuberculum olfactorium and striatum..
With the use of quantitative microspectrofluorometry, it has been shown that diazepam (10 mg/kg) and chlordiazepoxide (10 mg/kg) reduce DA turnover in the tuberculum olfactorium, nuc. It is of considerable interest that with a dose of 1 mg/kg of diazepam a reduction of DA turnover can still be observed in the tuberculum olfactorium and nuc.
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