Impaired fear inhibitory properties of GABA(A) and mu opioid receptors of the dorsal periaqueductal grey in alcohol-withdrawn rats

Autor(es)

Carmo Silva, Lais Batista ^{[1, 2]} ; Nobre, Manoel Jorge ^{[1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Inst Neurosci & Behav INeC, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Philosophy Sci & Letters, Psychobiol Lab, BR-14049 Ribeirao Preto, SP - Brazil

^[3] Uni FACEF, Dept Psychol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ACTA NEUROBIOLOGIAE EXPERIMENTALIS; v. 74, n. 1, p. 54-66, 2014.
• Citações Web of Science: 5

Resumo

The dorsal periaqueductal grey (DPAG) is a midbrain region that plays a fundamental role on the expression of the anxiety and fear-related responses. Increased fear and anxiety levels are the most frequent symptoms present in the alcohol withdrawal syndrome. This study aims to assess whether GABA and opioid receptors of the DPAG could be implicated in the expression of the conditioned fear state elicited in alcohol withdrawn-rats. For this purpose, we used the fear-potentiated startle (FPS) procedure. Drugs used were the selective GABA(A) agonist muscimol (1 nmol/0.2 mu l) and the predominantly mu opiate receptors agonist morphine (10 nmol/0.2 mu l). Exposure to aversive cues of the elevated-plus-maze (EPM) was used in order to validate the influence of alcohol withdrawal on emotionality. Data from FPS pointed out to an anxiogenic-like profile of withdrawal, a result sustained by the data collected from the EPM test. Muscimol and morphine showed their well-known anxiolytic-like profile, decreasing the fear-potentiated startle (FPS) amplitude in control subjects. However, the drugs had no effect on the levels of fear evoked in rats pre-treated with and withdrawn from alcohol. It is suggested that this lack of effect was possibly due to the desensitization of the GABA(A) receptors, as well as by the decrease on the responsiveness of the functions of mu opioid receptors, resulting from chronic administration of ethyl alcohol. These findings shed light on some aspects of the anxiety-like behavior elicited during alcohol withdrawal bringing new information on the influence of GABA and opioid receptors of the DPAG on the expression of unconditioned and conditioned fear responses. (AU)

• Processo FAPESP: 10/06165-3 - Efeitos da modulação farmacológica de receptores opióides e GABAérgicos da SCPD sobre a expressão do medo condicionado de ratos abstinentes de álcool, submetidos a estresse crônico, previamente selecionados por apresentarem alta ou baixa ansiedade
• Beneficiário: Laís Batista Carmo Silva
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 08/05724-9 - Neurobiologia do abuso de drogas: estudo comportamental e farmacológico sobre o medo e ansiedade eliciados em ratos abstinentes de álcool e morfina, e da importância de estruturas mesencefálicas na modulação dessas respostas
• Beneficiário: Manoel Jorge Nobre Do Espirito Santo
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/15157-4 - Ansiedade traço e enriquecimento ambiental como fatores determinantes no desenvolvimento e funcionamento do circuito de recompensa e aversão de ratos tornados dependentes de álcool ou morfina
• Beneficiário: Manoel Jorge Nobre Do Espirito Santo
• Linha de fomento: Auxílio à Pesquisa - Regular