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Conditioned fear is modulated by D(2) receptor pathway connecting the ventral tegmental area and basolateral amygdala

OLIVEIRA, Amanda Ribeiro de; REIMER, Adriano Edgar; MACEDO, Carlos Eduardo Antunes de; CARVALHO, Milene Cristina de; SILVA, Maria Angelica de Souza; BRANDAO, Marcus Lira
Fonte: ACADEMIC PRESS INC ELSEVIER SCIENCE Publicador: ACADEMIC PRESS INC ELSEVIER SCIENCE
Tipo: Artigo de Revista Científica
ENG
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Excitation of the mesocorticolimbic pathway, originating from dopaminergic neurons in the ventral tegmental area (VTA), may be important for the development of exaggerated fear responding. Among the forebrain regions innervated by this pathway, the amygdala is an essential component of the neural circuitry of conditioned fear. The functional role of the dopaminergic pathway connecting the VIA to the basolateral amygdala (BLA) in fear and anxiety has received little attention. In vivo microdialysis was performed to measure dopamine levels in the BLA of Wistar rats that received the dopamine D(2) agonist quinpirole (1 mu g/0.2 mu l) into the VTA and were subjected to a fear conditioning test using a light as the conditioned stimulus (CS). The effects of intra-BLA injections of the D(1) antagonist SCH 23390 (1 and 2 mu g/0.2 mu l) and D(2) antagonist sulpiride (1 and 2 mu g/0.2 mu l) on fear-potentiated startle (FPS) to a light-CS were also assessed. Locomotor performance was evaluated by use of open-field and rotarod tests. Freezing and increased dopamine levels in the BLA in response to the CS were both inhibited by intra-VTA quinpirole. Whereas intra-BLA SCH 23390 did not affect FPS, intra-BLA sulpiride (2 mu g) inhibited FPS. Sulpiride`s ability to decrease FPS cannot be attributed to nonspecific effects because this drug did not affect motor performance. These findings indicate that the dopamine D(2) receptor pathway connecting the ventral tegmental area and the basolateral amygdala modulates fear and anxiety and may be a novel pharmacological target for the treatment of anxiety. (C) 2010 Elsevier Inc. All rights reserved.; FAPESP[06/06354-5]; CNPq[472029/2006-0]; Deutsche Forschungsgemeischaft (DFG)[DFG DE 792/2-4]

Origem da inervação dopaminérgica da divisão central da amígdala expandida e da concha do núcleo Acumbens no rato.; Origin of dopaminergic fibers to the central extended amygdala and nucleus accumbens shell in the rat.

Hasue, Renata Hydee
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 23/01/2001 PT
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66.49%
A amígdala expandida central (EAc) inclui os núcleos central da amígdala (CeA), intersticial lateral da estria terminal (BSTl), intersticial do ramo posterior da comissura anterior (IPAC) e amígdala expandida sublenticular (SLEA). A EAc e a concha do acumbens possuem densa inervação dopaminérgica, implicada em processos motivacionais, e cuja origem foi estudada com a técnica de dupla marcação celular, combinando-se imunofluorescência para o traçador retrógrado Fluoro-Gold e para a tirosina hidroxilase. Nossos resultados indicam que a inervação dopaminérgica do CeA e BSTl é semelhante, se originando em igual proporção da área tegmental ventral (A10) e do núcleo dorsal da rafe/substância cinzenta periaquedutal (A10dc). A inervação dopaminérgica da SLEA, IPAC e concha do acumbens se origina principalmente do grupo A10. Com um anticorpo específico para dopamina vimos que parte da projeção do A10dc para o CeA é de fato dopaminérgica. Os grupos dopaminérgicos diencefálicos não inervam a EAc e a concha do acumbens.; The central extended amygdala (EAc) includes the central amygdaloid nucleus (CeA), lateral bed nucleus of the stria terminalis (BSTl), interstitial nucleus of the posterior limb of the anterior commissure (IPAC) and sublenticular extended amygdala (SLEA). The dopaminergic innervation of the EAc and nucleus accumbens shell is functionally related to motivational processes. Its origin was studied by combining immunofluorescence to tyrosine hydroxylase and Fluoro-Gold...

Envolvimento de receptores dopaminérgicos da área tegmental ventral e do complexo basolateral da amígdala na aquisição e na expressão do medo condicionado; Involvement of dopaminergic receptors of ventral tegmental area and basolateral amygdala in the acquisition and expression of conditioned fear

Oliveira, Amanda Ribeiro de
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 19/03/2010 PT
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96.69%
OLIVEIRA, A.R. Envolvimento de receptores dopaminérgicos da área tegmental ventral e do complexo basolateral da amígdala na aquisição e na expressão do medo condicionado. 2010. 93 f. Tese (Doutorado) Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo. O condicionamento Pavloviano é um dos paradigmas mais utilizados para estudar as bases biológicas das emoções, assim como da aprendizagem e memória. A dopamina (DA) é um dos principais neurotransmissores envolvidos na mediação de estados de medo e ansiedade. Um conjunto crescente de evidências dá suporte à hipótese de que a ativação da via mesocorticolímbica, proveniente de neurônios dopaminérgicos da área tegmental ventral (ATV), é particularmente sensível à estimulação aversiva. Entre as regiões inervadas por esta via, o complexo basolateral da amígdala (BLA) é um componente essencial dos circuitos neurais do medo condicionado. Assim, o presente estudo explorou o envolvimento de mecanismos DA da ATV e do BLA, através do uso de agonistas e antagonistas de receptores DA, na aquisição e expressão do medo condicionado à luz. Não houve efeito das drogas DA no sobressalto potencializado pelo medo (SPM), quando injetadas na ATV antes do condicionamento...

Organização das projeções da área tegmental ventral para o estriado. Um estudo no rato com a técnica de rastreamento anterógrado da leucoaglutina do Phaseolus vulgaris; Organization of ventral tegmental area projections to the striatum: an anterograde tracing study in the rat with the Phaseolus vulgaris leucoagglutinin technique

Lima, Leandro Bueno
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 14/04/2010 PT
Relevância na Pesquisa
96.69%
A área tegmental ventral (VTA) contém neurônios dopaminérgicos do grupamento A10 e envia projeções muito densas para o estriado ventral. Esta circuitaria está crucialmente envolvida em mecanismos de recompensa. Recentemente, a organização destas projeções foi reexaminada por Ikemoto S. (Brain Res. Rev., 56:27-78, 2007), em um estudo de rastreamento retrógrado minucioso, sendo proposto a subdivisão destas projeções em um sistema dopaminérgico mesoestriatal ventromedial que inerva a concha medial do accumbens e o tubérculo olfatório medial, e um sistema dopaminérgico mesoestriatal ventrolateral que inerva o cerne e a concha lateral do accumbens e o tubéculo olfatório lateral. Afim de complementar o conhecimento destas projeções, no presente estudo elas foram examinadas com a técnica anterógrada da leucoaglutinina do Phaseolus vulgaris. Nossos resultados indicam que há um extenso embricamento dos campos terminais estriatais inervados por diferentes setores/núcleos da VTA e reforçam a noção de que as eferências da VTA podem ser subdivididas em um sistema mesoestriatal ventromedial e um sistema mesoestriatal ventrolateral. Eles revelam ainda que as projeções da VTA para o estriado ventral têm uma organização topográfica médio-lateral mais complexa do que previamente reconhecido...

Envolvimento de mecanismos dopaminérgicos na expressão do medo condicionado contextual em ratos; Involvement of dopaminergic mechanisms in the expression of contextual conditioned fear in rats

Caetano, Kátia Alessandra de Souza
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 09/04/2012 PT
Relevância na Pesquisa
66.49%
É reconhecido que as experiências que geram reações de medo são praticamente indeléveis do encéfalo dos organismos e que condicionamentos aversivos suscitam inúmeras respostas defensivas, como o congelamento, sendo esta resposta um indicador de medo em roedores. Vários trabalhos têm apontado para a relação entre alterações na transmissão dopaminérgica e os estados aversivos. Entretanto, observam-se resultados conflitantes com a utilização de drogas dopaminérgicas em diferentes modelos animais de ansiedade. Assim, investigações devem ainda ser realizadas objetivando avaliar a funcionalidade da modulação dopaminérgica nos estados emocionais aversivos. O objetivo do presente estudo foi avaliar o envolvimento de mecanismos dopaminérgicos na expressão do medo condicionado ao contexto. Inicialmente foram avaliados os efeitos de agonistas (SKF 38393 e quimpirole) e antagonistas (SCH 23390 e sulpirida) de receptores D1 e D2 administrados sistemicamente sobre a expressão do medo condicionado contextual, sendo mensurado o tempo de congelamento dos animais. A atividade motora foi avaliada com o teste do campo aberto. Os resultados indicam que os receptores da família D2, e não D1, estão envolvidos na expressão do medo condicionado contextual...

Projeções diferenciadas da habênula lateral para o núcleo tegmental rostromedial e área tegmental ventral no rato.; Differential projections from the lateral habenula to the rostromedial tegmental nucleus and ventral tegmental area in the rat.

Gonçalves, Luciano
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 16/05/2013 PT
Relevância na Pesquisa
66.57%
O núcleo tegmental rostromedial (RMTg) é uma estrutura relé GABAérgica entre a habênula lateral (LHb) e a área tegmental ventral (VTA), que também recebe projeções diretas da LHb. Para detalhar a topografia das projeções da LHb para o RMTg e VTA, injeções de um traçador anterógrado foram depositadas na LHb. A origem das projeções da LHb para o RMTg e VTA foi confirmada com injeções de um traçador retrógrado, no RMTg ou VTA. Além disso, comparamos a posição topográfica dos neurônios marcados no RMTg após injeções na VTA, com os axônios marcados, vindas da LHb. Nossos dados revelaram que as projeções da LHb estão organizadas de maneira topográfica, com projeções para o RMTg, se originando da LHb lateral e as projeções para a VTA da LHb medial. No RMTg, axônios oriundos da LHb foram observados pertos de neurônios que se projetam para a VTA, formando aposições com esses neurônios. Os resultados indicam que as projeções da LHb para o RMTg e VTA originam-se de diferentes regiões da LHb e provam a existência de uma via bisináptica que conecta a LHb com a VTA via o RMTg.; The rostromedial segmental nucleus (RMTg) is a GABAergic relay between the lateral habenula (LHb) and the ventral tegmental area (VTA)...

Actions of orphanin FQ/nociceptin on rat ventral tegmental area neurons in vitro

Zheng, Fang; Grandy, David K; Johnson, Steven W
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/2002 EN
Relevância na Pesquisa
66.49%
Non-dopamine (putative GABAergic) neurons in the ventral tegmental area are in a position to influence mesolimbic functions by their inhibitory terminals that impinge locally on dopamine neurons and via their GABAergic efferents that innervate mesolimbic structures. In the present study we investigated responses of non-dopamine and dopamine neurons, recorded intracellularly in the rat midbrain slice, to orphanin FQ/nociceptin, the endogenous ligand for opioid receptor-like orphan receptors.When recording in either non-dopamine or dopamine neurons, orphanin FQ/nociceptin reduced the frequency of spike firing and caused membrane hyperpolarization under current-clamp, or produced outward current under voltage-clamp. Such responses were concentration-dependent and reversed at −108 mV and −102 mV in non-dopamine and dopamine neurons, respectively.Hyperpolarizations to orphanin FQ/nociceptin were not altered by tetrodotoxin or the opioid receptor antagonist naloxone, but were reduced by the opioid receptor-like orphan receptor antagonist [Phe11φCH2-NH)Gly2]NC(1–13)NH2 (1 μM).In dopamine neurons, orphanin FQ/nociceptin reduced the frequency of bicuculline- and tetrodotoxin-sensitive spontaneous inhibitory postsynaptic potentials, and reduced the amplitude of stimulus-evoked inhibitory postsynaptic potentials.Taken together...

Stimulation of the ventral tegmental area enhances the effect of vasopressin on blood pressure in conscious rats

van den Buuse, Maarten; Catanzariti, Renaldo
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/2000 EN
Relevância na Pesquisa
66.62%
The mesolimbic dopamine system projects to a large number of forebrain areas and plays an important role in the regulation of locomotor activity, cognition and reward. We previously found evidence for a functional interaction between the mesolimbic dopamine system and circulating vasopressin and the present study was performed to test the hypothesis that mesolimbic dopamine stimulation modulates the cardiovascular effects of vasopressin.Sprague-Dawley rats were stereotaxically implanted with a guide cannula into the region of origin of the mesolimbic system, the ventral tegmental area, and instrumented with catheters into the abdominal aorta and jugular vein. One week later, separate groups of conscious rats were injected intravenously with 1, 3 or 10 ng kg−1 of arginine-vasopressin or other vasopressor drugs before and after intra-ventral tegmental area injection of 10 nmol of neurotensin.Intra-ventral tegmental area injections of neurotensin had no significant effect on mean arterial pressure and heart rate but significantly potentiated the pressor response to intravenous administration of vasopressin when compared to saline-injections. However, the vasopressin-induced bradycardia was unaffected. Intravenous pretreatment with raclopride blocked the ability of neurotensin...

3α-HYDROXY-5α-PREGNAN-20-ONE IN THE MIDBRAIN VENTRAL TEGMENTAL AREA MEDIATES SOCIAL, SEXUAL, AND AFFECTIVE BEHAVIORS

FRYE, C. A.; RHODES, M. E.; PETRALIA, S. M.; WALF, A. A.; SUMIDA, K.; EDINGER, K. L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.62%
Progestins mediate the onset and duration of lordosis, the mating posture of female rodents, through actions in the hypothalamus and ventral tegmental area. In the hypothalamus, progesterone has traditional, “genomic” actions via intracellular progestin receptors. In the ventral tegmental area, 3α-hydroxy-5α-pregnan-20-one has “non-genomic” actions independent of progestin receptors to facilitate lordosis that involve GABAA/benzodiazepine receptors, NMDA type glutamate receptors, and/or dopamine receptors. 3α-Hydroxy-5α-pregnan-20-one levels also change with behavioral and/or environmental stimuli and may have a role in other reproductively-relevant behaviors, such as affiliation, exploration, and anxiety (socio-sexual behaviors). Data are reviewed that support the notion that: 1) effects of 3α-hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area facilitate lordosis and other reproductively-relevant behaviors. 2) 3α-Hydroxy-5α-pregnan-20-one, formed in the ventral tegmental area from metabolism of progestins, produced peripherally by endocrine glands, or centrally from biosynthesis in glial cells mediates socio-sexual behaviors. 3) 3α-Hydroxy-5α-pregnan-20-one’s actions at GABAA/benzodiazepine receptors...

Glutamate Synaptic Inputs to Ventral Tegmental Area Neurons in the Rat Derive Primarily from Subcortical Sources

Omelchenko, Natalia; Sesack, Susan R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.49%
Dopamine and GABA neurons in the ventral tegmental area project to the nucleus accumbens and prefrontal cortex and modulate locomotor and reward behaviors as well as cognitive and affective processes. Both midbrain cell types receive synapses from glutamate afferents that provide an essential control of behaviorally-linked activity patterns, although the sources of glutamate inputs have not yet been completely characterized. We used antibodies against the vesicular glutamate transporters VGlut1 and VGlut2 to investigate the morphology and synaptic organization of axons containing these proteins as putative markers of glutamate afferents from cortical versus subcortical sites, respectively. We also characterized the ventral tegmental area cell populations receiving VGlut1+ or VGlut2+ synapses according to their transmitter phenotype (dopamine or GABA) and major projection target (nucleus accumbens or prefrontal cortex). By light and electron microscopic examination, VGlut2+ as opposed to VGlut1+ axon terminals were more numerous, had a larger average size, synapsed more proximally, and were more likely to form convergent synapses onto the same target. Both axon types formed predominantly asymmetric synapses, although VGlut2+ terminals more often formed synapses with symmetric morphology. No absolute selectivity was observed for VGlut1+ or VGlut2+ axons to target any particular cell population. However...

Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat

Nair-Roberts, R.G.; Chatelain-Badie, S.D.; Benson, E.; White-Cooper, H.; Bolam, J.P.; Ungless, M.A.
Fonte: Elsevier Science Publicador: Elsevier Science
Tipo: Artigo de Revista Científica
Publicado em 09/04/2008 EN
Relevância na Pesquisa
66.66%
Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Within these midbrain regions and admixed with the dopamine neurons, are also substantial populations of GABAergic neurons that regulate dopamine neuron activity and have projection targets similar to those of dopamine neurons. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental area whose function remains unclear. Although dopamine neurons have been intensively studied and quantified, there is little quantitative information regarding the GABAergic and glutamatergic neurons. We therefore used unbiased stereological methods to estimate the number of dopaminergic, GABAergic and glutamatergic cells in these regions in the rat. Neurons were identified using a combination of immunohistochemistry (tyrosine hydroxylase) and in situ hybridization (glutamic acid decarboxylase mRNA and vesicular glutamate transporter 2 mRNA). 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. Thus...

Activity of Protein Kinase C is Important for 3α,5α-THP’s Actions at Dopamine Type 1-like and/or GABAA receptors in the Ventral Tegmental Area for Lordosis of Rats

Frye, Cheryl A.; Walf, Alicia A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.71%
In the ventral tegmental area, progestogens facilitate sexual receptivity of rodents via actions at dopamine type 1-like and/or γ-aminobutyric type A receptors and activation of downstream signal transduction molecules. In the present study, we investigated whether effects of progesterone’s metabolite, 3α,5α-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 γ-aminobutyric 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 3α,5α-THP-facilitated lordosis and its enhancement by dopamine type 1-like or γ-aminobutyric type A receptor agonists. Ovariectomized, E2 (10 μg s.c. at hr 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, 3α,5α-THP (100, 200 ng) or vehicle. Rats were pre-tested for lordosis and motor behavior and then tested for lordosis after each infusion and 10 and 60 mins after the last infusion. Rats were tested for motor behavior following their last lordosis test. As has been previously demonstrated...

Nicotinic and dopamine D2 receptors mediate nicotine-induced changes in ventral tegmental area neurotensin system

Alburges, Mario E.; Hoonakker, Amanda J.; Hanson, Glen R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.56%
Neuropeptides have been implicated in the psychopathology of stimulants of abuse. Neurotensin is a neuropeptide associated with the regulation of the nigrostriatal and mesolimbic dopamine pathways. In addition, the ventral tegmental area, a midbrain region implicated in the rewarding effects of most, if not all, addictive drugs, appears to be a particularly critical target for nicotine action. Because neurotensin has been linked with both mesolimbic and mesocortical dopamine function, we examined the impact of nicotine treatment on central nervous neurotensin systems by measuring changes in neurotensin tissue content because it has been shown such changes reflect alterations in release and activity of this peptide system. Male Sprague-Dawley rats received multiple administrations of (±) nicotine 4.0 mg/kg/day (0.8 mg/kg, i.p.; 5 × 2-h intervals) in the presence or absence of selective dopamine receptor antagonists (dopamine D1; SCH23390 or dopamine D2; eticlopride) or two doses of the non-selective nicotinic acetylcholine receptor antagonist (mecamylamine; 3.0 and 6.0 mg/kg, s.c.). The nicotine treatment significantly decreased neurotensin-like immunoreactivity content in the ventral tegmental area, as well as related regions such as prefrontal cortex...

Prominent activation of brainstem and pallidal afferents of the ventral tegmental area by cocaine

Geisler, Stefanie; Marinelli, Michela; DeGarmo, Beth; Becker, Mary L.; Freiman, Alexander J.; Beales, Mitch; Meredith, Gloria E.; Zahm, Daniel S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.53%
Blockade of monoamine transporters by cocaine should not necessarily lead to certain observed consequences of cocaine administration, including increased firing of ventral mesencephalic dopamine neurons and accompanying impulse-stimulated release of dopamine in the forebrain and cortex. Accordingly, we hypothesize that the dopaminergic activating effect of cocaine requires stimulation of dopaminergic neurons by afferents of the ventral tegmental area. We sought to determine if afferents of the ventral tegmental area are activated following cocaine administration. Rats were injected in the ventral tegmental area with retrogradely transported Fluoro-Gold and, after one week, were allowed to self-administer cocaine or saline via jugular catheters for two hours on six consecutive days. Other rats received like amounts of investigator-administered cocaine through jugular catheters. Afterward, the rats were killed and the brains processed immunohistochemically for retrogradely transported tracer and Fos, the protein product of the neuronal activation-associated immediate early gene, c-fos. Forebrain neurons exhibiting both Fos and tracer immunoreactivity were enriched in both cocaine groups relative to the controls only in the globus pallidus and ventral pallidum...

Activation of D2-like Receptors in Rat Ventral Tegmental Area Inhibits Cocaine-reinstated Drug-seeking Behavior

Xue, YueQiang; Steketee, Jeffery D.; Rebec, George V.; Sun, WenLin
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.66%
Relapse is a hallmark of cocaine addiction. Cocaine-induced neuroplastic changes in the mesocorticolimbic circuits critically contribute to this phenomenon. Preclinical evidence indicates that relapse to cocaine-seeking behavior depends on activation of dopamine neurons in the ventral tegmental area. Thus, blocking such activation may inhibit relapse. Because activity of dopamine neurons are regulated by D2-like autoreceptors expressed on somatodendritic sites, this study, using the reinstatement model, aimed to determine whether activation of D2-like receptors in the ventral tegmental area can inhibit cocaine-induced reinstatement of extinguished cocaine-seeking behavior. Rats were trained to self-administer intravenous cocaine (0.25 mg/infusion) under a modified fixed-ratio 5 schedule. After such behavior was well learned, rats went through extinction training to extinguish cocaine-seeking behavior. Then the effect of quinpirole, a selective D2-like receptor agonist microinjected into the ventral tegmental area on cocaine-induced reinstatement was assessed. Quinpirole (0 – 3.2 μg/side) dose-dependently decreased cocaine-induced reinstatement and such effects were reversed by the selective D2-like receptor antagonist eticlopride when co-microinjected with quinpirole into the ventral tegmental area. The effect appeared to be specific to the ventral tegmental area because quinpirole microinjected into the substantia nigra had no effect. Because D2-like receptors are expressed on rat ventral tegmental area dopamine neurons projecting to the prefrontal cortex and nucleus accumbens...

The mesopontine rostromedial tegmental nucleus: a structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta

Jhou, Thomas C.; Geisler, Stefanie; Marinelli, Michela; DeGarmo, Beth A.; Zahm, Daniel S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 20/04/2009 EN
Relevância na Pesquisa
66.52%
Prior studies revealed that aversive stimuli and psychostimulant drugs elicit Fos expression in neurons clustered above and behind the interpeduncular nucleus that project strongly to the ventral tegmental area (VTA) and substantia nigra (SN) compacta (C). Other reports suggest that these neurons modulate responding to aversive stimuli. We now designate the region containing them as the mesopontine rostromedial tegmental nucleus (RMTg) and report herein on its neuroanatomy. Dense mu opioid receptor and somatostatin immunoreactivity characterize the RMTg, as do neurons projecting to the VTA/SNC that are enriched in GAD 67 mRNA. Strong inputs to the RMTg arise in the lateral habenula (LHb) and, to a lesser extent, the SN. Other inputs come from the frontal cortex, ventral striatopallidum, extended amygdala, septum, preoptic region, lateral, paraventricular and posterior hypothalamus, zona incerta, periaqueductal gray, intermediate layers of the contralateral superior colliculus, dorsal raphe, mesencephalic, pontine and medullary reticular formation, and the following nuclei: parafascicular, supramammillary, mammillary, ventral lateral geniculate, deep mesencephalic, red, pedunculopontine and laterodorsal tegmental, cuneiform, parabrachial and deep cerebellar. The RMTg has meager outputs to the forebrain...

MK-801 infusions to the ventral tegmental area and ventromedial hypothalamus produce opposite effects on lordosis of hormone-primed rats

Petralia, Sandra M.; DeBold, Joseph F.; Frye, Cheryl A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.69%
Progesterone initiates female sexual behavior of rodents (lordosis) through actions at intracellular progestin receptors in the ventromedial hypothalamus. Progesterone’s metabolite, 5α-pregnan-3α-ol-20-one, mediates the intensity and duration of lordosis through its actions at GABAA receptors in the ventral tegmental area. Whether progestins can influence sexual behavior through actions that involve N-methyl-D-aspartate receptors (NMDARs) in the ventromedial hypothalamus and ventral tegmental area was investigated. The current study examines the effect of bilateral ventral tegmental area or ventromedial hypothalamus infusions of the non-competitive NMDAR antagonist (+)-MK-801 hydrogen maleate (MK-801; 0, 20, or 200 ng) on lordosis, motor activity, and NMDA R1 subtype (NMDAR1) immunoreactivity in estradiol benzoate (10 μg)+ progesterone (50 μg)- and estradiol benzoate+vehicle primed rats. Compared to vehicle infusions, infusions of MK-801 to the ventral tegmental area facilitated lordosis of estradiol benzoate (10 μg)+progesterone (50 μg)- and estradiol benzoate+vehicle primed rats. Infusions of MK-801 to the ventromedial hypothalamus inhibited lordosis of estradiol benzoate (10 μg)+progesterone (50 μg)- and estradiol benzoate+vehicle primed rats...

Timing and expectation of reward: a neuro-computational model of the afferents to the ventral tegmental area

Vitay, Julien; Hamker, Fred H.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 31/01/2014 EN
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66.57%
Neural activity in dopaminergic areas such as the ventral tegmental area is influenced by timing processes, in particular by the temporal expectation of rewards during Pavlovian conditioning. Receipt of a reward at the expected time allows to compute reward-prediction errors which can drive learning in motor or cognitive structures. Reciprocally, dopamine plays an important role in the timing of external events. Several models of the dopaminergic system exist, but the substrate of temporal learning is rather unclear. In this article, we propose a neuro-computational model of the afferent network to the ventral tegmental area, including the lateral hypothalamus, the pedunculopontine nucleus, the amygdala, the ventromedial prefrontal cortex, the ventral basal ganglia (including the nucleus accumbens and the ventral pallidum), as well as the lateral habenula and the rostromedial tegmental nucleus. Based on a plausible connectivity and realistic learning rules, this neuro-computational model reproduces several experimental observations, such as the progressive cancelation of dopaminergic bursts at reward delivery, the appearance of bursts at the onset of reward-predicting cues or the influence of reward magnitude on activity in the amygdala and ventral tegmental area. While associative learning occurs primarily in the amygdala...

Glutamatergic plasticity in medial prefrontal cortex and ventral tegmental area following extended-access cocaine self-administration

Ghasemzadeh, M. Behnam; Vasudevan, Preethi; Giles, Chad; Purgianto, Anthony; Seubert, Chad; Mantsch, John R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Glutamate signaling in prefrontal cortex and ventral tegmental area plays an important role in the molecular and behavioral plasticity associated with addiction to drugs of abuse. The current study investigated the expression and postsynaptic density redistribution of glutamate receptors and synaptic scaffolding proteins in dorsomedial and ventromedial prefrontal cortex and ventral tegmental area after cocaine self-administration. After 14 days of extended-access (6hr/day) cocaine self-administration, rats were exposed to one of three withdrawal regimen for 10 days. Animals either stayed in home cages (Home), returned to self-administration boxes with the levers withdrawn (Box), or underwent extinction training (Extinction). Extinction training was associated with significant glutamatergic plasticity. In dorsomedial prefrontal cortex of the Extinction group, there was an increase in postsynaptic density GluR1, PSD95, and actin proteins; while postsynaptic content of mGluR5 receptor protein decreased and there was no change in NMDAR1, Homer1b/c, or PICK1 proteins. These changes were not observed in ventromedial prefrontal cortex or ventral tegmental area. In ventral tegmental area, Extinction training reversed the decreased postsynaptic density NMDAR1 protein in the Home and Box withdrawal groups. These data suggest that extinction of drug seeking is associated with selective glutamatergic plasticity in prefrontal cortex and ventral tegmental area that include modulation of receptor trafficking to postsynaptic density.

Aferências hipotalâmicas para a área tegmental ventral, núcleo tegmental rostromedial e núcleo dorsal da rafe.; Hypothalamic afferents to the ventral tegmental area, rostromedial tegmental nucleus and dorsal rafe nucleus.

Lima, Leandro Bueno
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 23/06/2015 PT
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O hipotálamo modula comportamentos relacionados à motivação, recompensa e punição através de projeções para a área tegmental ventral (VTA), o núcleo dorsal da rafe (DR) e o núcleo tegmental rostromedial (RMTg). Nesse estudo, investigamos através de métodos de rastreamento retrógrado as entradas hipotalâmicas da VTA, do DR e do RMTg e, se neurônios hipotalâmicos individuais inervam mais do que uma dessas regiões. Também determinamos uma possível assinatura GABAérgica ou glutamatérgica das aferências hipotalâmicas, através de rastreamento retrógrado combinado com métodos de hibridação in situ. Observamos que VTA, DR e RMTg recebem um padrão bastante semelhante de entradas hipotalâmicas originando de neurônios de projeção glutamatérgicas e GABAérgicas, a maioria deles (> 90%) inervando somente um desses três alvos. Nossos achados indicam que entradas hipotalâmicas são importantes fontes de sinais homeostáticos para a VTA, o DR e o RMTg. Eles exibem um alto grau de heterogeneidade que permite de excitar ou inibir as três estruturas de forma independente ou em conjunto.; The hypothalamus modulates behaviors related to motivation, reward and punishment via projections to the ventral tegmental area (VTA)...