Allopregnanolone does not influence ethanol-induced conditioned place preference in DBA/2J mice.

摘要

RATIONALE: The neurosteroid allopregnanolone (ALLOP; 3alpha-hydroxy-5alpha-pregnan-20-one) produces behavioral and discriminative characteristics similar to that of ethanol (EtOH) and can modulate some of the behavioral and electrophysiological effects of EtOH. OBJECTIVE: The present experiments investigated ALLOP modulation of the effects of EtOH in a place conditioning procedure in male DBA/2J mice. METHODS: In a series of experiments examining different EtOH doses (1, 2 g/kg) and ALLOP administration times, ALLOP (0, 3.2, 10, 17 mg/kg, i.p.) was administered four times with EtOH prior to placement on a distinctive floor (CS+). On alternate days, vehicle was administered prior to a saline injection paired with the other floor stimulus (CS-). In a separate experiment, finasteride (0, 50, 100 mg/kg, i.p.), a 5alpha-reductase inhibitor that blocks ALLOP synthesis, was administered prior to both CS+ and CS- trials. In a final experiment, animals were place conditioned to EtOH alone, and ALLOP (0, 3.2, 10, 17 mg/kg, i.p.) was administered prior to the preference test only. RESULTS: During conditioning, ALLOP increased and finasteride decreased EtOH-stimulated activity compared with vehicle pretreatment. Acquisition of 2 g/kg EtOH-induced conditioned place preference was observed in all mice, regardless of treatment with either ALLOP or finasteride. Similarly, ALLOP did not modulate the expression of EtOH-induced place preference. EtOH increased brain ALLOP levels compared with saline; however, ALLOP administration produced dose-dependent elevations in brain ALLOP levels that were not further augmented by EtOH (2 g/kg) administration. CONCLUSIONS: These findings indicate that ALLOP does not modulate EtOH-induced place conditioning in male DBA/2J mice.