GABA(A) receptors modulate ethanol-induced conditioned place preference and taste aversion in mice

Rationale: GABAA receptor antagonists have been shown to reduce ethanol sel f-administration and ethanol-induced conditioned taste aversion (CTA) in ra ts, suggesting a role for the GABA, receptor in modulating ethanol's motiva tional effects. Objectives: The present experiments examined the effects of the GABA(A) receptor antagonists, bicuculline and picrotoxin, on the acqui sition of ethanol-induced conditioned place preference (CPP) and CTA in mal e DBA/2J mice. Methods: Mice in the CPP experiments received four pairings of ethanol (2 g/kg) with a distinctive floor stimulus for a 5-min condition ing session (CS+ sessions). During CS+ sessions, mice also received bicucul line (0, 1.0, 3.0, or 5.0 mg/kg) or picrotoxin (2.0 mg/kg) before an inject ion of ethanol. On intervening days (CS- sessions), the pretreatment inject ion was always vehicle followed by saline injections that were paired with a different floor type. For the preference test, all mice received saline i njections and were placed on a half grid and half hole floor for a 60-min s ession. For the CTA experiments, mice were adapted to a 2-h per day water r estriction regimen followed by five conditioning trials every 48 h. During conditioning trials, subjects received an injection of vehicle, bicuculline (0.5 and 2.0 mg/kg), or picrotoxin (0.75 and 2.5 mg/kg) before injection o f 2 g/kg ethanol or saline following l-h access to a saccharin solution. Re sults: Both picrotoxin and the lowest dose of bicuculline (1.0 mg/kg) signi ficantly increased the magnitude of CPP relative to vehicle-treated control s. Picrotoxin alone did not produce place conditioning. Ethanol-stimulated locomotor activity was significantly reduced during conditioning trials wit h picrotoxin and the higher doses of bicuculline (3.0 and 5.0 mg/kg). Bicuc ulline did not alter ethanol-induced CTA; however, picrotoxin dose-dependen tly increased the magnitude of ethanol-induced CTA. Bicuculline and picroto xin did not produce CTA when administered alone. Conclusions: Overall, thes e results suggest that blockade of GABA, receptors with bicuculline and pic rotoxin enhances ethanol's motivational effects in the CPP paradigm; howeve r, only picrotoxin enhances ethanol's motivational effects in the CTA parad igm.