Pentylenetetrazol produces a state-dependent conditioned place aversion to alcohol withdrawal in mice.

The purpose of this study was to determine if aversive effects of alcohol withdrawal could be detected in mice using the place conditioning procedure and whether the GABA(A) receptor antagonist, pentylenetetrazol (PTZ), would increase the aversive effects of alcohol withdrawal and increase the probability of detecting conditioned place aversion. Subjects were alcohol-naïve mice from a specific line selectively bred for low alcohol preference (LAP1; n=91) and were assigned to three groups: alcohol withdrawal, PTZ alone, and PTZ+alcohol withdrawal. On four trials, mice received either a 4.0 g/kg intraperitoneal (i.p.) injection of alcohol (alcohol withdrawal, PTZ+alcohol withdrawal groups) or saline (PTZ group) 8 h prior to being placed on a distinctive floor texture for a 30-min conditioning session. Five minutes before these sessions, mice in the PTZ and PTZ+alcohol withdrawal groups received PTZ (5.0 mg/kg; i.p.) and the alcohol withdrawal group received saline. On intervening days mice received two saline injections at the same time points prior to being placed on a different floor texture. Post-conditioning floor preference was assessed in two 60-min tests; the first test was drug-free and the second test was state-dependent. Neither alcohol withdrawal nor PTZ produced significant place conditioning. The PTZ+alcohol withdrawal group showed a significant place aversion during the state-dependent test. These data suggest that the combined stimulus properties of PTZ and alcohol withdrawal facilitated the expression of conditioned place aversion to alcohol withdrawal.