Chronic benzodiazepine administration facilitates the subsequent development of ethanol dependence

This study investigated the effect of chronic benzodiazepine (BZD) administration and its abrupt discontinuation on later subsequent ethanol consumption employing a free choice paradigm between water and increasing ethanol concentrations. In addition, we also studied the anxiolytic and reinforcing properties of ethanol assessed in the elevated plus maze (EPM) and in the conditioned place preference paradigm, respectively. Adult male Wistar rats were subjected to a chronic diazepam (DZM) treatment (2 mg/kg/day, i.p.) during 21 days. Twenty-four hours after that treatment and, in another experiment, 10 days after the last DZM injection, rats were subjected to an oral ethanol self-administration procedure (ethanol was increased in concentration (v/v) on 4 consecutive days as follows: 2%, 4%, 6%, 8% followed by an additional period of 8 days in which animals were offered a 10% (v/v) ethanol solution. Diazepam treated rats showed a higher ethanol intake and spontaneous signs of ethanol withdrawal when the access to ethanol was discontinued. These results were observed when ethanol was available at day 1 of withdrawal but not when DZM treated rats were initiated in the ethanol choice test 10 days after BDZ withdrawal. Furthermore, DZM treated rats exhibited an increased anxiolytic ethanol induced effect (1 g/kg, i.p.) in the EPM and a significant ethanol-induced conditioned place preference (1 g/kg, i.p.). These data suggest that early DZM treatment facilitates ethanol consumption and the development of ethanol dependence.