Impaired fear inhibitory properties of GABAA and μ opioid receptors of the dorsal periaqueductal grey in alcohol-withdrawn rats.

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opioid receptors of the DPAG could be implicated in the expression of the conditioned fear state elicited in alcohol withdrawn-rats.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 GABAA agonist muscimol (1 nmol/0.2 μL) and the predominantly mu opiate receptors agonist morphine (10 nmol/0.2 μL). 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 However, the drugs had no effect on the levels of fear evoked in rats pre-treated with and withdrawn from alcohol.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 GABAA receptors, as well as by the decrease on the responsiveness of the functions of μ 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.