Intrahippocampal nicotine and neurosteroids effects on the anxiety-like behaviour in voluntary and chronic alcohol-drinking rats

Considerable evidence suggests that the anxiolytic effects of ethanol may be one of the factors that promotes alcohol consumption. The present study aimed to characterize the effects of intrahippocampal administrations of nicotine and the two neurosteroids pregnenolone sulphate (PregS) and allopregnanolone (AlloP) on anxiety-like behaviours in alcohol-drinking rats. A long-lasting free-choice drinking procedure with an early availability (from weaning) of an alcoholic solution (10% (v/v) ethanol, 3% (w/v) glucose in distilled water) was used. After 80 days of consumption, alcohol-drinking and control rats were deprived of food and assigned at random to six groups. After 100 days of consumption, each group received two consecutive intrahippocampal (dorsal CA1) injections. First injection: nicotine (4.6 μg, 20 mM) or saline; second injection: PregS (5 ng, 24 μM), AlloP (0.2 μg, 1.26 μM) or saline. Following the injections, novelty-directed activity (open field, OF), and motor coordination (80° inclined screen) were tested. Blood alcohol concentrations (BACs) were assessed. Anxiolytic-like effects of voluntary ethanol consumption and intrahippocampal AlloP administration were observed. Alcohol intake increased the novelty-induced ambulation and exploration of central areas, and decreased defecation. The high exploration levels induced by AlloP decreased significantly over sessions, indicating a rapid habituation to the environmental conditions. Motor coordination was deteriorated by ethanol consumption. These results demonstrate the effects of chronic alcohol intake and neurosteroid administration on anxiety-related behaviours, and suggest an important role of the hippocampal GABAA receptor in these behaviours.