Impaired fear inhibitory properties of GABA(A) and mu opioid receptors of the dorsal periaqueductal grey in alcohol-withdrawn rats

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: ACTA NEUROBIOLOGIAE EXPERIMENTALIS; v. 74, n. 1, p. 54-66, 2014.
• Web of Science Citations: 5

Abstract

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opioid receptors of the DPAG could be implicated in the expression of the conditioned fear state elicited in alcohol withdrawn-rats.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 However, the drugs had no effect on the levels of fear evoked in rats pre-treated with and withdrawn from alcohol.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)

• FAPESP's process: 10/15157-4 - Trait anxiety and environmental enrichment as determining factors on the development and functioning of the reward and aversion circuitry in rats made dependent on alcohol or morphine
• Grantee: Manoel Jorge Nobre Do Espirito Santo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/06165-3 - Effects of opioid and GABaergic modulation of the dPAG neurons on the conditioned fear of rats tested under alcohol withdrawal, submitted to chronic stress, and previously selected for their low or high anxiety levels
• Grantee: Laís Batista Carmo Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 08/05724-9 - Neurobiology of Drug Abuse: A behavioural and pharmacological study on fear and anxiety elicited in alcohol and morphine withdrawn rats, and the role of mesencephalic structures on the modulation of these responses.
• Grantee: Manoel Jorge Nobre Do Espirito Santo
• Support Opportunities: Regular Research Grants