GABAA receptors modulate ethanol-induced conditioned place preference and taste aversion in mice |
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Authors: | J A Chester Christopher L Cunningham |
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Institution: | (1) Department of Behavioral Neuroscience, and Portland Alcohol Research Center, Oregon Health Sciences University, Portland, OR, 97201-3098, USA, US |
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Abstract: |
Rationale: GABAA receptor antagonists have been shown to reduce ethanol self-administration and ethanol-induced conditioned taste aversion
(CTA) in rats, suggesting a role for the GABAA receptor in modulating ethanol’s motivational effects. Objectives: The present experiments examined the effects of the GABAA receptor antagonists, bicuculline and picrotoxin, on the acquisition of ethanol-induced conditioned place preference (CPP)
and CTA in male 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 conditioning
session (CS+ sessions). During CS+ sessions, mice also received bicuculline (0, 1.0, 3.0, or 5.0 mg/kg) or picrotoxin (2.0
mg/kg) before an injection of ethanol. On intervening days (CS– sessions), the pretreatment injection was always vehicle followed
by saline injections that were paired with a different floor type. For the preference test, all mice received saline injections
and were placed on a half grid and half hole floor for a 60-min session. For the CTA experiments, mice were adapted to a 2-h
per day water restriction 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 of 2 g/kg ethanol
or saline following 1-h access to a saccharin solution. Results: Both picrotoxin and the lowest dose of bicuculline (1.0 mg/kg) significantly increased the magnitude of CPP relative to
vehicle-treated controls. Picrotoxin alone did not produce place conditioning. Ethanol-stimulated locomotor activity was significantly
reduced during conditioning trials with picrotoxin and the higher doses of bicuculline (3.0 and 5.0 mg/kg). Bicuculline did
not alter ethanol-induced CTA; however, picrotoxin dose-dependently increased the magnitude of ethanol-induced CTA. Bicuculline
and picrotoxin did not produce CTA when administered alone. Conclusions: Overall, these results suggest that blockade of GABAA receptors with bicuculline and picrotoxin enhances ethanol’s motivational effects in the CPP paradigm; however, only picrotoxin
enhances ethanol’s motivational effects in the CTA paradigm.
Received: 12 September 1998 / Final version: 21 December 1998 |
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Keywords: | Alcohol DBA/2J Reward Aversion GABA Place conditioning Taste conditioning |
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