engleski

Bicucculine antagonizes the effects of dehydroepiandrosterone on rat behavior

Neurosteroid dehydroepiandrosterone (DHEA) has been associated with various functions in the central nervous system including memory and behavior ; however its mechanisms of action are not fully understood. The behavioral profile of DHEA was investigated in rats in the forced swim test (FST) and active avoidance (AA) paradigm, as well as its impact on the locomotor activity. Male Wistar rats received DHEA (2, 10, and 50 mg/kg) or vehicle intraperitoneally, 30 min prior testing. The capability of bicuculline (0.5, 1, and 2 mg/kg) to antagonize effects of DHEA was checked. 10 mg/kg of DHEA significantly decreased the duration of immobility in FST, suggesting antidepressant-like effects and facilitated the retrieval of avoidance responses in AA testing. At higher doses (50 mg/kg) DHEA performance in the retention session was attenuated. These effects were antagonized by bicuculline (2 mg/kg), a specific GABAA receptor antagonist. DHEA did not show significant effects on struggling behavior, locomotor activity, habituation crossings and intertrial crossings. Hence, DHEA in a manner resembling an inverted U shape, facilitated retrieval of memory task imposed to rats in AA, suggesting enhanced formation of implicit, procedural and hippocampal-independent memory task. In addition, data suggest that DHEA might have triggered antidepressant-like effects in rats. The observed actions of DHEA were not confounded by change in motor function, but were abolished with bicuculline, confirming partially GABA-ergic mediation of the effects. However, the molecular and neuronal substrates linking the actions of DHEA to specific GABAA receptors remain to be further elucidated and linked to human neuropsychiatric disorders.

dehydroepiandrosterone ; Wistar rats ; forced swim test ; active avoidance ; motor activity ; bicuculline

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