Ten-week-old male C57BL/6J mice were surgically implanted bilaterally with guide cannulae directed between the substantia nigra and ventral tegmental area. 
In this study, using RT-PCR, activation of Homer1a mRNA transcription in response to acute and repeated administration of cocaine was characterized in prefrontal cortex, nucleus accumbens, and ventral tegmental area, three mesocorticolimbic nuclei of the rat brain.
One to three hours after 4 mg/kg acute methamphetamine (METH) administration, the levels of Nurr1 mRNA were significantly higher in the prelimbic (PrL), primary motor (M1) and primary somatosensory (S1) cortices and ventral tegmental area (VTA), as compared with the basal level.
Because high densities of alpha3beta4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area.
Dopaminergic projections from the ventral tegmental area (VTA) constitute the mesolimbocortical system that underlies addiction and psychosis primarily as the result of increased dopaminergic transmission.
We show that the bed nucleus of the stria terminalis (BNST) efficient relays cortical excitation to dopamine neurons of the ventral tegmental area (VTA).
In B6 wild-type mice ventral tegmental area (VTA) pre-treatment with the muscarinic receptor antagonist atropine (3 microg bilateral), but not the nicotinic receptor antagonist mecamylamine (5 microg bilateral), reduced locomotion in response to 30 mg/kg morphine to a similar extent as systemic M5 knockout, suggesting that reduced morphine-induced locomotion in M5 knockout mice is due to the loss of M5 receptors on VTA dopamine neurons.
Using immunohistochemistry, PPARgamma distribution and its co-localization with neuron-specific protein markers were investigated in rat and mouse brain sections spanning the hypothalamus, the ventral tegmental area (VTA) and the nucleus tractus solitarius (NTS).
Herein, we examined a new method for intervention in depressive states based on deep brain stimulation of the ventral tegmental area (VTA) as a source of incentive motivation and hedonia, in comparison to chemical antidepressants.
The avian substantia nigra and ventral tegmental area, however, showed specific labeling.
METHODS: Functional magnetic resonance imaging (fMRI) hemodynamic responses to novelty and reward (monetary incentive) from the substantia nigra/ventral tegmental area (SN/VTA), the nucleus accumbens (NAcc), and the hippocampus of 29 subjects were correlated with novelty-seeking scores.
Furthermore, lesioning with 6-hydroxydopamine of the ventral tegmental area (VTA), the origin of mesolimbic dopaminergic neurons, resulted in attenuated BLA-DG LTP.
Here, we performed the selective gene rescue of functional beta2*-nAChRs in either the substantia nigra pars compacta (SNpc) or the ventral tegmental area (VTA) of beta2KO mice.
Fos was measured as a marker of neuronal activation in the ventral bed nucleus of the stria terminalis (BNSTv) and ventral tegmental area (VTA).
Background: Ghrelin, an orexigenic peptide, acts on growth hormone secretagogue receptors (GHS-R1A), expressed in the hypothalamus as well as in important reward nodes such as the ventral tegmental area.
Synaptic transmission onto dopaminergic neurons of the mammalian ventral tegmental area (VTA) can be potentiated by acute or chronic exposure to addictive drugs.
We found that covering one eye blocked visually induced IEG expression throughout both contralateral visual pathways of the brain, and reduced activation of the contralateral ventral tegmental area, a non-visual midbrain motivation-related area affected by social context.
ABSTRACT: The midbrain dopaminergic (mDA) neurons of the substantia nigra and the ventral tegmental area play a fundamental role in the control of voluntary movement and the regulation of emotion, and are severely affected in Parkinson's disease.
The lesion decreased the number of TH (+) cells of the pars compacta of substantia nigra by 33%, without modifying the number of TH (+) cells in ventral tegmental area.
Regression analyses showed a positive association between cue-elicited craving and ventral tegmental area (VTA) activation in response to heroin-related stimuli in heroin-dependent patients.
Among other biochemical adaptations, chronic exposure to abused drugs decreases the expression of insulin receptor substrate-2 (IRS-2; a protein involved in neurotrophic signaling) in the ventral tegmental area (VTA), a neural substrate for many drugs of abuse.
RESULTS: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra.
The progesterone metabolite and neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) has actions in the midbrain ventral tegmental area (VTA) to modulate lordosis, but its effects on other reproductively-relevant behaviors are not well understood.
These behaviors are mediated by dopaminergic neurons originating from the ventral tegmental area (VTA), and long-term changes of these dopaminergic neurons are attributed to increased postsynaptic glutamatergic activation.
Using in situ hybridization, we examined the mRNA expression of 5-hydroxytryptamine transporter (5-HTT) and 5-hydroxytryptamine 1A receptor (5-HT1AR) in 3 crucial regions in addiction, namely the ventral tegmental area (VTA), the nucleus accumbens (NAc), and the medial prefrontal cortex (mPFC), during the dependence and withdrawal.
Systemic administration of selective 5-HT1A agonists, such as 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT), stimulates the electrical activity of ventral tegmental area (VTA) dopamine neurons by a mechanism which remains unknown.
The midbrain dopamine (DA) neuron system consists of the retrorubral area (A8), the substantia nigra (SN; A9) and the ventral tegmental area (VTA; A10).
We assessed the presence of degenerating neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) of parkinsonian monkeys.
Binding studies show upregulation of high-affinity nAChRs after 21 days of treatment in cortical areas, caudate putamen, nucleus accumbens, hippocampus, ventral tegmental area, and superior colliculi.
Highly relevant to these functions, orexin-containing neurons from the lateral hypothalamus project densely to the ventral tegmental area (VTA), which is the origin of dopamine projections implicated in motivation and reward.
Here we challenge the view that reward-guided learning is solely controlled by the mesoaccumbens pathway arising from dopaminergic neurons in the ventral tegmental area and projecting to the nucleus accumbens.
Recent studies indicate that RGS proteins also modulate the coupling efficiency between gamma-aminobutyric acid type B (GABA(B)) receptors and GIRK channels in dopamine neurons of the ventral tegmental area (VTA), the initial target for addictive drugs in the brain reward pathway.
The influence of intra-ventral tegmental area administration of gamma-amino-butyric-acid-B (GABA(B)) receptor agonist and antagonist on the expression and acquisition of morphine-induced conditioned place preference (CPP) in morphine-sensitized female rats was examined. In conclusion, results confirmed the importance of GABA(B) receptors within the ventral tegmental area of morphine CPP in morphine-sensitized female rats..
Projections from the ventral tegmental area (VTA) have been demonstrated to terminate in the prefrontal cortex (PFC) and to be dopaminergic and/or gamma-aminobutyric acidergic (GABAergic), forming a neural circuit implicated in certain memory and cognitive processes.
In this study, we traced the efferent axonal projections from ventral tegmental area (VTA) to forebrain structures, an integrating part of the reward circuit implicated in drug addiction, in rats using MEMRI.
The progesterone metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP, allopregnanolone), acts in the ventral tegmental area (VTA) to facilitate exploratory, anti-anxiety, and socio-sexual behavior among ovariectomized (OVX), estrogen (E(2))-primed rats and gonadally-intact rats with high (proestrus) or low (diestrus) endogenous E(2) levels.
Acute (0.3 mg/kg or 0.5 mg/kg i.p.) and chronic nicotine, as well as morphine (15 mg/kg s.c.) in control mice decreased nipecotic acid-induced increase in extracellular GABA in the substantia nigra/ventral tegmental area (VTA/SN).
Recently we showed that in midbrain slices, acute ethanol exposure facilitates glutamatergic transmission onto dopaminergic neurons in the ventral tegmental area (VTA).
Synaptic plasticity in the ventral tegmental area (VTA) has been implicated in the acquisition of a drug-dependent state.
In the present study, we assessed the role of CB1 receptors within the key regions of the mesolimbic dopamine pathway, the nucleus accumbens (NAcc) and ventral tegmental area (VTA), in regulation of ethanol self-administration.
ventral tegmental area (VTA) dopamine (DA) neurons have long been implicated in many drug-related behaviors, including alcohol self-administration.
RESULTS: The nicotine treatment significantly but temporarily decreased substance P-like immunoreactivity (SPLI) content in the ventral tegmental area (VTA) and substantia nigra 12-18 h after drug exposure.
On the other hand, DA cells in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) do not change their mean firing rate across the sleep-wake cycle.
It is well known that the ventral tegmental area (VTA) is a brain region in which virtually all abused drugs exert rewarding effects by activating its dopamine neurons.
It has long been known, at least in mammals, that the central serotonergic system modulates the activity of dopaminergic neurons in both the nigrostriatal pathway and ventral tegmental area.
The main control seems to be inhibitory, this effect being more marked in the ventral tegmental area (VTA) as compared to the substantia nigra pars compacta (SNc).
With antibodies raised against the N-terminal mouse EAAT4 sequence, the highest protein expression levels were observed in the substantia nigra pars compacta, ventral tegmental area, paranigral nucleus, habenulo-interpeduncular system, supraoptic nucleus, lateral posterior thalamic nucleus, subiculum, and superficial layers of the superior colliculus.
Microdialysis was used to assess the contribution to cocaine seeking of cholinergic input to the mesocorticolimbic dopamine system in ventral tegmental area (VTA).
However, when these measures are taken alone they do not predict DA content in ventral tegmental area (VTA) neurons.
Within the ventral tegmental area (VTA), the interaction of DA with ACh appears to be integral in mediating motivated behaviors.
Mice fed a HF diet for twenty weeks were obese, hyperphagic and had decreased CB1 receptor binding levels in the substantia nigra (12.8%) and ventral tegmental area (17.1%) compared to the LF controls.
Using functional connectivity, we show that the DS and the VS are differentially connected to different midbrain regions (possibly corresponding to the substantia nigra [ SN] and the ventral tegmental area [ VTA], respectively).
Brainstem afferents arise bilaterally from the ventral tegmental area, substantia nigra, central gray, A8, locus coeruleus, ventral subcoeruleus nucleus, and raphe nuclei.
This pathway originates in the ventral tegmental area (VTA) and terminates in the nucleus accumbens (NAcc) where dopamine is increased by nicotine but decreased during withdrawal.
It is well known that during the male rat sexual interaction different levels of arousal or sexual motivation are involved and that these motivational changes are associated with variations in the level of dopamine (DA); however, it is not yet known if these changes are associated with a different functionality of the nucleus Accumbens (Acc) and ventral tegmental area (VTA), neural structures that constitute the DA mesoaccumbens system.
Nociceptin/orphanin FQ (N/OFQ) has been reported to inhibit dopamine (DA) release in basal ganglia mainly by acting on NOP receptors in substantia nigra and ventral tegmental area.
The rewarding effects of drugs of abuse are thought to be dependent on the mesocorticolimbic dopamine system, which originates in the ventral tegmental area (VTA) and projects into the nucleus accumbens (NAC) and other forebrain regions.
The results demonstrate that PR is transiently expressed within the first 2 weeks of life in specific motor, sensory and reticular core nuclei as well as within midbrain dopaminergic cell groups such as the substantia nigra and the ventral tegmental area.
Alcoholic patients showed slightly reduced signal changes in the brain stem adjacent to ventral tegmental area (VTA) and in the ventromedial prefrontal cortex (VMPFC) during the reward task, while we found no alterations in the right and left ventral striatum (VS).
The present study was conducted to examine the effects of prolonged bupropion administration on the firing activity of dorsal raphe nucleus (DRN), locus coeruleus (LC), and ventral tegmental area (VTA) neurons.
In normal pups from P5 to P15, only 1-2% of neurons containing TH mRNA in the ventral tegmental area (VTA) and substantia nigra, pars compacta, also displayed VGLUT2 mRNA.
It is known that dopamine (DA) neurons in the ventral tegmental area (VTA) and norepinephrine (NE) neurons in the locus ceruleus (LC) are autoregulated by somatodendritic D(2)-like and alpha(2)-adrenoceptors, respectively.
The effects of 2-d and 21-d administration of three MAOIs were investigated (clorgyline, selective MAOI-A; deprenyl, selective MAOI-B; phenelzine, non-selective MAOI) on the firing activity of DA neurons in the ventral tegmental area using in-vivo electrophysiology in rats.
Dopamine neurons in the ventral tegmental area (VTA) play a very important role in a variety of physiological as well as addictive behaviors.
Rats were trained to press a lever to deliver electrical stimulation to the substantia nigra (SNc)/ventral tegmental area (VTA) after the random onset of a cue that predicted reward availability.
We report an anatomical abnormality of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) in different strains of inbred and outbred mice, one mouse strain (C57BL/6, B6) from different commercial suppliers, and in B6J mice bred internally.
Considerable evidence implicates the mesolimbic dopamine (DA) system in the processing of nicotine's reinforcing properties, specifically the ventral tegmental area (VTA) and the terminal fields of VTA DAergic projections to the "core" (NAcore) and "shell" (NAshell) subdivisions of the nucleus accumbens (NAc).
Activation of striatum and ventral tegmental area was enhanced to positive feedback signaled by a smiling face, but this was reduced in participants with avoidant attachment, indicating relative impassiveness to social reward.
Stress exposure increased BDNF mRNA levels in the ventral tegmental area (VTA) and nucleus accumbens (NAc) only in cocaine-experienced mice following a prolonged, but not acute, drug-free period.
While glutamate transmission onto dopamine cells in the ventral tegmental area undergoes transient plasticity important for establishing addiction-related behaviors, glutamatergic plasticity in the nucleus accumbens is critical for the expression of these behaviors.
In the ventral tegmental area, progestogens facilitate sexual receptivity of rodents via actions at dopamine type 1-like and/or gamma-aminobutyric acid type A receptors and activation of downstream signal transduction molecules. In the present study, we investigated whether effects of progesterone's metabolite, 3alpha,5alpha-THP, to enhance lordosis via actions at these receptors in the ventral tegmental area requires phospholipase C-dependent protein kinase C. The objective of this study was to test the hypothesis that: if progestogens' actions through dopamine type 1-like and/or gamma-aminobutyric acid type A receptors in the ventral tegmental area for lordosis require protein kinase C, then inhibiting protein kinase C in the ventral tegmental area should reduce 3alpha,5alpha-THP-facilitated lordosis and its enhancement by dopamine type 1-like or gamma-aminobutyric acid type A receptor agonists. at h 0)-primed rats were tested for their baseline lordosis responses and then received a series of three infusions to the ventral tegmental area: first, bisindolylmaleimide (75 nM/side) or vehicle; second, SKF38393 (100 ng/side), muscimol (100 ng/side), or vehicle; third, 3alpha,5alpha-THP (100, 200 ng/side) or vehicle. As has been previously demonstrated, 3alpha,5alpha-THP infusions to the ventral tegmental area increased lordosis and effects were further enhanced by infusions of SKF38393 and muscimol. Infusions of bisindolylmaleimide to the ventral tegmental area attenuated 3alpha,5alpha-THP-, SKF38393-, and/or muscimol-facilitated lordosis. Thus, 3alpha,5alpha-THP's actions in the ventral tegmental area through membrane receptors may require activity of protein kinase C..
This basal forebrain structure receives dopamine (DA) input from the ventral tegmental area (VTA) and glutamate (GLU) input from regions including the prefrontal cortex (PFC), amygdala (AMG), and hippocampus (HIP).
Excitatory inputs from the pedunculopontine nucleus interact with timed inhibitory inputs from model striosomes in the ventral striatum to regulate dopamine burst and dip responses from cells in the substantia nigra pars compacta and ventral tegmental area.
Infusion of the Group II metabotropic glutamate receptor antagonist LY341495 into the medial prefrontal cortex enhanced glutamate release in this region, the nucleus accumbens and the ventral tegmental area in sensitized animals, compared to controls, following short-term withdrawal but not after long-term withdrawal.
We have found that progestogen-facilitated lordosis of rodents is enhanced by activation of dopamine type 1 (D(1)) or GABA(A) receptors and their downstream effectors, such as second messengers, in the ventral tegmental area (VTA).
Oxytocin (80 ng) injected into the caudal mesencephalic ventral tegmental area (VTA) of male rats induces penile erection.
Dopamine, corticosteroids, oxytocin, vasopressin, and opioids form the neurochemical substrate for pair bonding in areas like the nucleus accumbens, the prefrontal cortex, the piriform cortex, the medial preoptic area, the ventral tegmental area and the medial amygdala, among others.
A last group of MSDB mice received additional bilateral guide cannulae targeting the ventral tegmental area (VTA) or a more dorsal region to assess the effects of intra-VTA injection of SCH23390 on intra-MSDB muscimol self-administration.
It is known that the ventral tegmental area (VTA) is necessary for induction, and expression involves the nucleus accumbens (NAc).
Using in vivo extracellular recordings from identified ventral tegmental area dopamine (DA) neurons, we report that amphetamine-sensitized rats display an activation of ventral hippocampal neuron firing and a significantly greater number of spontaneously active DA neurons compared with saline-treated rats.
Lesioning of dopaminergic neurons in the ventral tegmental area resulted in an impaired performance in the reference memory task, whereas the execution of the working memory tasks appeared to be unaffected in the Morris water maze.
Although ventral tegmental area (VTA) dopamine (DA) neurons represent a crucial component of this system, the synaptic adaptations underlying natural rewards and drug-related motivation have not been fully elucidated.
RESULTS: Our results demonstrate altered reward pathway activation along the nucleus accumbens-hypothalamic-ventral tegmental area circuitry resulting from overexpression of DeltaFosB in the nucleus accumbens and striatal regions.
Recent studies showed that LH orexin neurons that project to ventral tegmental area (VTA) have greater Fos induction in association with elevated morphine preference during protracted withdrawal than non-VTA-projecting orexin neurons, indicating that the VTA is an important site of action for orexin's role in reward processing.
Finally, animals prenatally exposed to MDMA and examined on postnatal day 35 showed an increase in tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra but not in the ventral tegmental area.
Changes in synaptic strength on ventral tegmental area (VTA) dopamine neurons are thought to play a critical role in the development of addiction-related behaviors.
It is well established that the behavioral sensitization is based on the augmentation of the mesocorticolimbic dopaminergic activity originating in the ventral tegmental area of the midbrain that project to the nucleus accumbens, the medial prefrontal cortex and other forebrain regions.
Drugs of abuse including nicotine acutely modulate the activity of mesolimbic dopaminergic neurons, projecting from the ventral tegmental area of the midbrain to the nucleus accumbens (NAc).
The reward system contains the ventral tegmental area, nucleus accumbens and ventral pallidum and finally sends information to the lateral hypothalamic area, the feeding center. The dopaminergic system originating from the ventral tegmental area mediates the motivation to consume palatable food.
We then summarize results from pharmacological and neuroanatomical studies on the role of several neurotransmitter systems (dopamine, glutamate, serotonin and opioids) and brain areas (ventral tegmental area, accumbens shell, dorsal striatum, basolateral amygdala, prefrontal cortex, dorsal hippocampus and lateral hypothalamus) in context-induced reinstatement.
Preclinical research in animal models of the various aspects of nicotine dependence suggests a critical role of glutamate, gamma-aminobutyric acid (GABA), cholinergic and dopamine neurotransmitter interactions in the ventral tegmental area and possibly other brain sites, such as the central nucleus of the amygdala and the prefrontal cortex, in the effects of nicotine.
Reward-seeking behavior is controlled by neuronal circuits that include the basolateral nucleus of amygdala (BLA), medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and ventral tegmental area.
Recent evidence suggests that dopaminergic neurons of the ventral tegmental area (VTA) play a key role in the manifestation of stress vulnerability.
Importantly, in the midbrain region, LRRK2 protein was preferentially expressed in A9 DA neurons of the substantia nigra, compared to A10 DA neurons of the ventral tegmental area.
In contrast and at all the time points of extinction, binding to DAT was significantly enhanced in CONT animals when compared to SALINE and NON-CONT rats in different forebrain and mesencephalic regions, including the nucleus accumbens, ventral tegmental area or caudate putamen.
Analysis of neural activation across 39 brain regions using Fos immunohistochemistry showed the following results: (1) VEHICLE-SOCIAL and VEHICLE-ALONE groups did not differ in Fos expression, indicating that a social context per se did not affect Fos expression, (2) MDMA-treated groups showed significantly increased Fos expression relative to VEHICLE treated groups in 30 brain regions, (3) the MDMA-SOCIAL group showed augmented Fos expression relative to the MDMA-ALONE group in six brain regions including the caudate-putamen (medial), medial preoptic area, paraventricular thalamic nucleus, central amygdala, ventromedial hypothalamic nucleus, and the medial amygdala (posterodorsal), and (4) the MDMA-SOCIAL group (but not the MDMA-ALONE group) showed augmented Fos expression relative to the VEHICLE groups in the nucleus accumbens, ventral tegmental area and periaqueductal grey.
BACKGROUND: Addiction has been considered a disorder of motivational control over behavior, and the ventral tegmental area (VTA), in conjunction with other limbic brain structures, is thought to play a critical role in the regulation of a number of motivated behaviors including seeking of addictive drugs such as alcohol.
We have previously reported a reduction of somatic withdrawal symptoms in alphaCGRP knock-out mice exposed to chronic nicotine, leading us to investigate the contribution of alphaCGRP to the regulations of ventral tegmental area (VTA) neurons and their response to nicotine.
Measures of TH and DBH were quantified in song control regions (HVC, Area X, robust nucleus of the acropallium) and regions implicated in motivation (medial preoptic nucleus (POM), ventral tegmental area (VTA), and midbrain central gray).
We will discuss DA/5-HT interactions at the level of receptors and G protein-coupled potassium channels and consequences for induction of depolarization blockade with specific attention to DA neurons in the ventral tegmental area (VTA) and the substantia nigra zona compacta (SN), neurons implicated in treatment efficacy and the side-effects of schizophrenia, respectively.
On the other hand, drugs selectively acting on dopaminergic transmission produced modest changes in extracellular DA in mPFC, and had no effect on the occipital or parietal cortex.Acute administration of morphine did not increase DA levels in the PFC (where NA is diminished), in contrast with augmented dopaminergic neuronal activity; moreover, during morphine withdrawal both DA and NA levels increased, in spite of a diminished dopaminergic activity, both increases being antagonised by clonidine but not quinpirole administration.Extensive 6-hydroxy dopamine lesion of the ventral tegmental area (VTA) decreases below 95% of control both intra- and extracellular DA and DOPAC in the nucleus accumbens, but only partially or not significantly in the mPFC and parietal cortex.The above evidence points to a common origin for NA and DA in the cerebral cortex and suggests the possible utility of noradrenergic system modulation as a target for drugs with potential clinical efficacy on cognitive functions..
The dopaminergic neurons of the ventral tegmental area (DA VTA neurons) are important for the rewarding and reinforcing properties of drugs of abuse, including ethanol.
However, to date there are no in vivo data on how structural parameters of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic projections, relate to memory performance in healthy young and older adults.
Nicotine-induced effects on dopamine in the dorsal and ventral hippocampus (VH), prefrontal and medial temporal cortex, and superior cerebral peduncle were lower in the young than in adult, the same in the ventral tegmental area (VTA) and lateral septal nucleus (LS), and somewhat higher in the nucleus accumbens shell (NAccS).
Glutamatergic input to the ventral tegmental area contributes to this activation: in animals trained to self-administer cocaine, cocaine-predictive cues trigger ventral tegmental glutamate release and dopaminergic activation.
There is a preferential loss of dopamine (DA) neurons in the ventral tier of the substantia nigra (vtSN) compared to the dorsal tier and ventral tegmental area (VTA) in PD.
In the present work using a [ (3)H]-labeled derivative of the heptapeptide we have identified and characterized [ (3)H]-SP(1-7) binding in the rat ventral tegmental area (VTA).
In several brain areas, ethanol depresses glutamatergic excitatory transmission, but how it affects excitatory synapses on dopamine neurons of the ventral tegmental area (VTA), a crucial site for the development of drug addiction, is not known.
These included the ventral tegmental area/substantia nigra regions, the striatum, and frontal lobe regions involved in (1) emotion processing (medial prefrontal, anterior cingulate, and insula cortex), (2) cognition (dorsolateral prefrontal cortex), and (3) motor/behavioral outputs (primary motor area).
The medial PFC, as well as the ventral tegmental area, also seem to participate in the generation of pelvic thrusting..
Injections of anterograde tracer into the PPN led to intense fiber labeling in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA).
When the ability to use environmental information or external cues is lost as well, significant cell loss in the ventral tegmental area, with reduced DA-innervation of the mesocorticolimbic regions and the nucleus accumbens, must be suspected.
The progesterone (P(4)) metabolite and neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) acts in the midbrain ventral tegmental area (VTA) to modulate lordosis of female rats.
In control rats intravenously administered clozapine (0.078-10 mg/kg) increased the firing rate and the burst firing activity of dopamine (DA) neurons in the ventral tegmental area (VTA).
RATIONALE: Progesterone (P(4)) has actions in the ventral tegmental area (VTA) to regulate female sexual behavior in rodents.
The current study investigated whether ethanol alters ATP activation of purinergic type 2 receptors (P2Rs) in the ventral tegmental area (VTA).
We recently found that the interfering peptide Tat-3L4F is able not only to disrupt the protein-protein interaction of PTEN (phosphatase and tensin homologue deleted on chromosome 10) with the serotonin 5-HT2C receptor in the rat ventral tegmental area (VTA) but also to suppress the conditioned place preference induced by cannabinoid and nicotine without significant effects on anxiety, feeding behavior and motor activity.
Melatonin MT1 and MT2 receptors are G protein coupled receptors which are expressed in various parts of the CNS (suprachiasmatic nuclei, hippocampus, cerebellar cortex, prefrontal cortex, basal ganglia, substantia nigra, ventral tegmental area, nucleus accumbens and retinal horizontal, amacrine and ganglion cells) and in peripheral organs (blood vessels, mammary gland, gastrointestinal tract, liver, kidney and bladder, ovary, testis, prostate, skin and the immune system).
A lesser density of hFF2 neurons was identified in the ventromedial hypothalamic nucleus, lateral and posterior hypothalamic areas whereas few cells were visualized in the paraventricular hypothalamic nucleus, perifornical nucleus, horizontal limb of the diagonal band, ventral division of the bed nucleus of the stria terminalis, nucleus basalis of Meynert and ventral tegmental area.
Initial effects of drugs of abuse seem to converge on the mesolimbic dopamine pathway originating from the ventral tegmental area (VTA).
Very high binding occurs in brain regions associated with dopaminergic reward (nucleus accumbens, ventral tegmental area) and motor (substantia nigra, caudate/putamen) systems.
Previous results show that axons that support self-stimulation travel between the PM and the ventral tegmental area (VTA) and that their activation increases firing of VTA neurons.
Morphometric analysis of the TH-ir neurons of the substantia nigra (SN) and ventral tegmental area (VTA) was performed using an appropriate image analysis system.
Wfs1-positive nerve fibers were found in the medial forebrain bundle, reticular part of the substantia nigra, globus pallidus, posterior caudate putamen, lateral lemniscus, alveus, fimbria, dorsal hippocampal commissure, subiculum, and to a lesser extent in the central sublenticular extended amygdala, compact part of substantia nigra, and ventral tegmental area.
Adult male Sprague-Dawley rats received injections of CTAP into the caudate putamen, the rostral or caudal ventral tegmental area (VTA) or the medial shell or core of the nucleus accumbens prior to cocaine to determine the role of mu opioid receptors in cocaine-induced reward and hyperactivity.
To study the regional and cellular distribution of xeroderma pigmentosum group A and B (XPA and XPB) proteins, two nucleotide excision repair (NER) factors, in the mammalian brain we used immunohistochemistry and triple fluorescent immunostaining combined with confocal microscope scanning in brain slices of adult rat brain, including the cerebral cortex, striatum, substantia nigra compacta, ventral tegmental area, red nucleus, hippocampus, and cerebellum.
Alcohol exerts reinforcing effects on cortico-mesolimbic dopamine pathways through the disinhibition of the inhibitory effects of gamma-amino-butyric acid-A neurons in the ventral tegmental area.
Previously, we demonstrated that the action of the natural alkaloid, ibogaine, to reduce alcohol (ethanol) consumption is mediated by the glial cell line-derived neurotrophic factor (GDNF) in the ventral tegmental area (VTA).
After Gdnf ablation, mice showed a progressive hypokinesia and a selective decrease of brain tyrosine hydroxylase (Th) mRNA, accompanied by pronounced catecholaminergic cell death, affecting most notably the locus coeruleus, which practically disappears; the substantia nigra; and the ventral tegmental area.
The ventral tegmental area is part of the midbrain dopamine system and is crucially involved in reward, motivation and drug abuse. In the present manuscript we determined the role of presynaptic metabotropic glutamate receptors (mGluRs) in the regulation of spontaneous glutamate release of terminals projecting to dopamine cells in the ventral tegmental area of mice.
The following thirteen regions were identified by the stepwise discriminant analysis of the z-scores as significantly contributing to the differences between the sham and OBX: amygdala, cingulate cortex, caudate putamen at the level of globus pallidus, caudate putamen-lateral part, dorsal subiculum, dorsal thalamus, hypothalamus, median raphe, somatosensory cortex, substantia nigra, ventral hippocampus, ventral tegmental area and the ventral thalamus. The pattern of changes in the rCGU following OBX does not completely correlate with the pattern of connectivity of the olfactory bulbs, however, many regions with direct connection to the olfactory bulbs (e.g., amygdala, hypothalamus, ventral hippocampus, and ventral tegmental area) were found to be important for differentiation.
We tested insulin efficacy within the medial hypothalamic arcuate (ARC) and paraventricular (PVN) nuclei, the nucleus accumbens, and the ventral tegmental area. However, although the mu opioid DAMGO, [ D-Ala2,N-MePhe4,Gly5-ol]-enkephalin acetate salt, stimulated sucrose intake at all four CNS sites, the ventral tegmental area was the only sensitive site for a direct effect of insulin to antagonize acute (60 min) micro opioid-stimulated sucrose feeding: sucrose intake was 53+/-8% of DAMGO-induced feeding, when insulin was coadministered with DAMGO.
This study determined the role of ventral tegmental area acetylcholine and glutamate receptors in modulating laterodorsal tegmentum stimulation-evoked dopamine efflux in the nucleus accumbens. Intraventral tegmental area infusions of the muscarinic acetylcholine receptor antagonist scopolamine, the nicotinic acetylcholine receptor antagonist mecamylamine, or the ionotropic glutamate receptor antagonist kynurenate significantly diminished dopamine efflux in the nucleus accumbens evoked by brief electrical stimulation of the laterodorsal tegmentum. These findings suggest that acetylcholine and ionotropic glutamate receptors influence rapid dopaminergic activity and thus the communication of behaviorally relevant information from ventral tegmental area dopamine cells to forebrain areas..
OBJECTIVES: To explore the potential role of ovarian hormones in the regulation of dopamine (DA) neuron firing activity in ventral tegmental area (VTA) induced by acute cocaine in intact female or ovariectomized (OVX) rats.
Using in-vivo electrophysiological and behavioural paradigms in the rat, the effects of bifeprunox and aripiprazole were assessed on ventral tegmental area (VTA) dopamine and dorsal raphe serotonin (5-HT) cell activity and on foot shock-induced ultrasonic vocalisation (USV).
To further clarify this mechanism, single-unit recording with fine glass electrodes was used in awake rats to examine responses of ventral tegmental area (VTA) neurons, both presumed dopamine (DA) and non-DA, to iv cocaine and tail-press, a typical somato-sensory stimulus.
The ventral tegmental area (VTA) is a brain region implicated in drug addiction and related behaviors; however, little research has been conducted examining the role of the VTA in these processes in adolescent rats.
Furthermore, we immunohistochemically examined the ventral tegmental area (VTA), which is the origin of hippocampal dopaminergic fibers using tyrosine hydroxylase (TH), a marker enzyme for the dopaminergic nervous system.
In a detailed immunohistochemistry study, we show that OCT3 is expressed in aminergic pathways in the mouse brain, particularly in dopaminergic neurons of the substantia nigra compacta, non-aminergic neurons of the ventral tegmental area, substantia nigra reticulata (SNr), locus coeruleus, hippocampus and cortex.
In the midbrain, numerous Lmx1b-expressing neurons were present in the substantia nigra pars compacta and ventral tegmental area.
In the present study, we examined whether ventral tegmental area (VTA) stimulation or environmental enrichment altered the severity of lipopolysaccharide (LPS)-induced sickness behaviors and the provocation of cytokine expression induced by the endotoxin.
A number of peptides with effects on hypothalamic function also modulate the mesolimbic dopamine system (ventral tegmental area and nucleus accumbens).
To examine whether the dopaminergic system is activated by N(2)O, frozen sections of the ventral tegmental area of rats exposed to 75% N(2)O were double-stained for c-Fos and tyrosine hydroxylase. RESULTS: Exposure to 75% N(2)O increased c-Fos expression in tyrosine hydroxylase-positive cells in the ventral tegmental area.
The number and morphology of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and ventral tegmental area were determined stereologically. The number of tyrosine hydroxylase-positive cells in rats fed the n-3 PUFA-deficient diet was 33.9% lower in the substantia nigra pars compacta and 33.7% lower in the ventral tegmental area than in those fed the control diet (P<0.05); however, the volume of tyrosine hydroxylase-positive cell bodies was not different between diet groups in either brain region.
Similar to mammals, the avian Ac and MSt receive glutamatergic input from the pallium and dopaminergic input from the substantia nigra and ventral tegmental area.
CB1-R antagonist or agonist administered into the ventral tegmental area (VTA) equally suppressed or stimulated feeding respectively, in both genotypes.
Withdrawal from morphine leads to the appearance of extreme anxiety accompanied of several physical disturbances, most of them linked to the activation of brainstem regions such as the locus coeruleus, ventral tegmental area, hypothalamic nuclei and periaqueductal grey (PAG).
Ex vivo autoradiography in rats has shown that high level of [ (125)I]PE2I accumulates in the striatum and also in the substantia nigra and ventral tegmental area.
In the present study, the effects of bilateral intra-ventral tegmental area (intra-VTA) injections of an anticholinesterase, physostigmine and/or muscarinic acetylcholine receptor antagonist, atropine on memory retention and morphine state-dependent learning were examined in adult male Wistar rats.
Because the CRF-BP is implicated in neurotransmission within the ventral tegmental area (VTA), we investigated whether the CRF-BP is expressed in VTA neurons.
We therefore determined the effects of nicotine self-administration and extinction on NMDA-induced glutamate neurotransmission between the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA).
Detailed analyses of these 42 genes in the nucleus accumbens, ventral tegmental area, nucleus of the solitary tract, lateral hypothalamus, arcuate, paraventricular, ventromedial and dorsomedial nuclei suggests that molecules involved in feeding stimulation and termination are coexpressed in multiple consumption-related sites.
The levels of alpha-synuclein mRNA remained unchanged in all brain regions examined (the striatum, nucleus accumbens, amygdala, substantia nigra, ventral tegmental area).
We investigated in the rat the relative effects of selective bilateral partial lesions of substantia nigra pars compacta (SNc) or ventral tegmental area (VTA) which did not affect locomotion, on fine motor, motivational and cognitive behaviors.
Long-term potentiation (LTP) of excitatory synapses on ventral tegmental area (VTA) dopamine (DA) cells is thought to play an important role in mediating some of the behavioral effects of drugs of abuse yet little is known about its underlying mechanisms.
Microinjection of mu-opioid agonist endomorphin-1 (1-10 microg) given into the ventral tegmental area dose-dependently increased the release of the extracellular dopamine in the posterior nucleus accumbens shell in the urethane-anesthetized rats. The increased dopamine caused by endomorphin-1 (10 microg) was completed blocked by the (+)-morphine (10 pg) pretreatment given into ventral tegmental area.
Furthermore, we tested the effect of local intra-cerebral micro-infusions of WIN into the nucleus accumbens (NAc), ventral tegmental area (VTA), dorsal (dHIP) and ventral (vHIP) hippocampus and medial prefrontal cortex (mPFC).
Substantial evidence indicates that mu-opioid receptors (MORs) modulate dopamine transmission in the ventral tegmental area (VTA).
In the present study, the possible role of nicotinic acetylcholine (nACh) receptors of the ventral tegmental area (VTA) on morphine-state-dependent learning was studied in adult male Wistar rats.
The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction.
Rewards such as food, sex, and drugs influence this system in part by modulating dopamine neurotransmission in the mesolimbic dopamine reward circuit, including the ventral tegmental area (VTA) and the ventral striatum (NAc).
The alterations of serine 897 phosphorylations of NR1 receptors in the striatum and ventral tegmental area of after-conditioning rats were measured immunochemically. Although the alterations induced by KET were not significant in most areas we studied, MA showed a significant increase in the ventral tegmental area but a marked decrease in caudate putamen and nucleus accumbens.
Silencing urokinase in the ventral tegmental area in vivo induces changes in cocaine-induced hyperlocomotion.
Using immunohistochemistry, c-Fos, a marker of cell activation, was quantified in the nucleus accumbens (Acb), lateral hypothalamus (LH), ventral tegmental area (VTA), and locus coeruleus (LC).
BACKGROUND: Activation of the dopaminergic (DA) neurons of the ventral tegmental area (VTA) by ethanol has been implicated in its rewarding and reinforcing effects.
With this aim, we have systematically reviewed the main findings of most of the existing literature that explores cross-talk in the five brain areas that are most traditionally implicated in addiction: amygdala, prefrontal cortex, nucleus accumbens, hippocampus and ventral tegmental area (VTA).
In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor.
A post mortem biochemical analysis revealed a decrease in serotonin content in the prelimbic and infralimbic cortices, caudate-putamen (but not nucleus accumbens), globus pallidus and substantia nigra-ventral tegmental area, as well as a decrease in dopamine content in the caudate-putamen in STN-lesioned compared with sham rats.
Drugs of abuse acutely modulate the activity of mesolimbic dopaminergic neurons, projecting from the ventral tegmental area of the midbrain to the nucleus accumbens (NAc).
CCK gene expression was higher in hippocampus, amygdala, and prefrontal cortex, but lower in the ventral tegmental area of HR relative to LR rats.
Increases in D2 binding sites, presumably involving GABAergic projection neurons, were measured in the nucleus accumbens, olfactory tubercle and ventral tegmental area of the 5-HT1B KO.
In the rat, an endogenous ADP/ATPergic tone reinforces the release of dopamine from the axon terminals in the nucleus accumbens as well as from the somatodendritic region of these neurons in the ventral tegmental area, as well as the release of glutamate, probably via P2Y(1) receptor stimulation.
The MSt, but not Area X, projects to the ventral tegmental area (VTA) and SNc, but neither MSt nor Area X projects to the SNr.
Neurons in midbrain dopamine centers, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), densely innervate Area X and show singing-related changes in firing rate.
c-Fos expression was significantly elevated in neglectful relative to nurturing mothers in the CNS, particularly within dopamine associated areas, such as the zona incerta (ZI), ventral tegmental area (VTA), and nucleus accumbens.
Cholinergic stimulation of dopamine neurons in the ventral tegmental area (VTA) underlies activation of the brain reward circuitry.
Brain sites that have been implicated in the mediation of addictive cannabinoid properties include primarily the ventral tegmental area, the nucleus accumbens, and the medial prefrontal cortex, although the amygdala, the substantia nigra, the globus pallidus, and the hippocampus have also been shown to be critical structures mediating motivational and reinforcing effects of cannabinoids.
The origin of this reward-related activity is not clear, although dopaminergic ventral tegmental area neurons project to M1, where they are thought to inhibit output neurons and could be the source of the finding.
Application of ethanol in the nAc results in elevated dopamine levels in the same brain region, whereas administration in the anterior ventral tegmental area (VTA) fails to influence dopamine output.
morphine in the nucleus accumbens and guanosine-5'-o-(3-[ (35)S]thio) triphosphate ([ (35)S]GTPgammaS) binding to membranes of the ventral tegmental area (VTA) induced by DAMGO.
Alcohol-preferring (P) rats, stereotaxically implanted with bilateral guide cannulae into the nucleus accumbens, ventral tegmental area, and the central nucleus of the amygdala were given 30% alcohol and water in a 24h voluntary two-bottle choice paradigm. The data show reduced alcohol intake by 32-49.5% after 100-pmol glycyl-glutamine into reward sites (nucleus accumbens, ventral tegmental area, and central nucleus of the amygdala), but not after injections into control sites dorsal to reward sites. The order of sensitivity to the 1-fmol dose was amygdala > or = ventral tegmental area > accumbens.
The ventral tegmental area (VTA) is a nodal link in reward circuitry.
Chronic abuse of cocaine is known to cause neuroadaptive changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA).
Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental area whose function remains unclear. In substantia nigra pars compacta 29% of cells were glutamic acid decarboxylase mRNA-positive, 58% in the retrorubral field and 35% in the ventral tegmental area. There were further differences in the relative sizes of the GABAergic populations in subnuclei of the ventral tegmental area. Vesicular glutamate transporter 2 mRNA-positive neurons were present in the ventral tegmental area, but not substantia nigra or retrorubral field. They were mainly confined to the rostro-medial region of the ventral tegmental area, and represented approximately 2-3% of the total neurons counted ( approximately 1600 cells).
Here, we analyzed the cell viability of neural systems related to the pathophysiology of depression after DD, including NA-LC, serotoninergic-raphe nuclei and dopaminergic-ventral tegmental area neurons, and evaluated the depressive behavioral profile of light-deprived rats.
The mesolimbic dopamine system including the ventral tegmental area, nucleus accumbens (NAc) and associated brain regions such as the amygdala (AMG) are proposed to be involved in the behavioral sensitization.
We previously found that glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA) negatively regulates alcohol drinking (He, D.
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