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 GABAA 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 hrs prior to being placed on a distinctive floor texture for a 30-min conditioning session. Five min 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

Effects of Alcohol on the Acquisition and Expression of Fear Potentiated Startle in Mouse Lines Selectively Bred for High and Low Alcohol Preference

Rationale: Anxiety disorders and alcohol-use disorders frequently co-occur in humans perhaps because alcohol relieves anxiety. Studies in humans and rats indicate that alcohol may have greater anxiolytic effects in organisms with increased genetic propensity for high alcohol consumption. Objectives and Methods: The purpose of this study was to investigate the effects of moderate doses of alcohol (0.5, 1.0, 1.5 g/kg) on the acquisition and expression of anxiety-related behavior using a fear-potentiated startle (FPS) procedure. Experiments were conducted in two replicate pairs of mouse lines selectively bred for high- (HAP1 and HAP2) and low- (LAP1 and LAP2) alcohol preference; these lines have previously shown a genetic correlation between alcohol preference and FPS (HAP\u3eLAP; Barrenha and Chester 2007). In a control experiment, the effect of diazepam (4.0 mg/kg) on the expression of FPS was tested in HAP2 and LAP2 mice. Results: The 1.5 g/kg alcohol dose moderately decreased the expression of FPS in both HAP lines but not LAP lines. Alcohol had no effect on the acquisition of FPS in any line. Diazepam reduced FPS to a similar extent in both HAP2 and LAP2 mice. Conclusions: HAP mice may be more sensitive to the anxiolytic effects of alcohol than LAP mice when alcohol is given prior to the expression of FPS. These data collected in two pairs of HAP/LAP mouse lines suggest that the anxiolytic response to alcohol in HAP mice may be genetically correlated with their propensity toward high alcohol preference and robust FPS