The discriminative stimulus properties of self-administered ethanol are mediated by GABA(A) and NMDA receptors in rats.

Hodge, Clyde W. and Cox, Amy A. and Bratt, Alison M. and Camarini, Rosana and Kelley, Stephen P. and Mehmert, Kirstin K. and Nannini, Michelle A. and Olive, M. Foster (2001) The discriminative stimulus properties of self-administered ethanol are mediated by GABA(A) and NMDA receptors in rats. Psychopharmacology, 154 . pp. 13-22. (doi:10.1007/s002130000619) (Full text available)

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Abstract

RATIONALE: The neurobiological systems that mediate the discriminative stimulus effects of self-administered drugs are largely unknown. The present study examined the discriminative stimulus effects of self-administered ethanol. METHODS: Rats were trained to discriminate ethanol (1 g/kg, IP) from saline on a two-lever drug discrimination task with sucrose (10% w/v) reinforcement. Test sessions were conducted with ethanol (0 or 10% v/v) added to the sucrose reinforcement to determine if self-administered ethanol would interact with the discriminative stimulus effects of investigator-administered ethanol, or with the ethanol-like discriminative stimulus effects of the GABAA-positive modulator pentobarbital or the non-competitive NMDA antagonist MK-801. RESULTS: During a saline test session, ethanol (10% v/v) was added to the sucrose reinforcement. Responding by all animals began accurately on the saline-appropriate lever and then switched to the ethanol-appropriate lever after rats self-administered a mean dose of 1.2 +/- 0.14 g/kg ethanol. During cumulative self-administration trials, responding initially occurred on the saline lever and then switched to the ethanol-appropriate lever after ethanol (0.68 +/- 0.13 g/kg) was self-administered. Investigator-administered MK-801 (0.01-1.0 mg/kg, cumulative IP) and pentobarbital (0.3-10.0 mg/kg, cumulative IP) dose-dependently substituted for ethanol. When ethanol (10% v/v) was added to the sucrose reinforcer, MK-801 and pentobarbital dose-response curves were shifted significantly to the left. CONCLUSIONS: Self-administered ethanol substituted for and potentiated the stimulus effects of investigator-administered ethanol, suggesting that the discriminative stimulus effects of self-administered ethanol are similar to those produced by investigator-administered ethanol. Self-administered ethanol enhanced the ethanol-like discriminative stimulus effects of MK-801 and pentobarbital, which suggests that the discriminative stimulus effects of self-administered ethanol are mediated by NMDA and GABAA receptors.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Q Science > QP Physiology (Living systems)
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Stephen Kelley
Date Deposited: 29 Jun 2011 17:07
Last Modified: 13 Dec 2015 04:20
Resource URI: https://kar.kent.ac.uk/id/eprint/11702 (The current URI for this page, for reference purposes)
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