Current address: Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80303.
The Nicotinic Acetylcholine Receptor Partial Agonist Varenicline Increases the Ataxic and Sedative-Hypnotic Effects of Acute Ethanol Administration in C57BL/6J Mice
Version of Record online: 14 OCT 2010
Copyright © 2010 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 34, Issue 12, pages 2053–2060, December 2010
How to Cite
Kamens, H. M., Andersen, J. and Picciotto, M. R. (2010), The Nicotinic Acetylcholine Receptor Partial Agonist Varenicline Increases the Ataxic and Sedative-Hypnotic Effects of Acute Ethanol Administration in C57BL/6J Mice. Alcoholism: Clinical and Experimental Research, 34: 2053–2060. doi: 10.1111/j.1530-0277.2010.01301.x
- Issue online: 18 NOV 2010
- Version of Record online: 14 OCT 2010
- Received for publication January 20, 2010; accepted May 26, 2010.
- Nicotinic Acetylcholine Receptors;
Background: The costs associated with alcohol abuse are staggering, therefore much effort has been put into developing new pharmacologic strategies to decrease alcohol abuse. Recently, the nicotinic acetylcholine receptor (nAChR) partial agonist varenicline has been shown to decrease ethanol consumption in both humans and animal models.
Methods: We examined the effects of varenicline on the ataxic and sedative-hypnotic effects of ethanol. First, varenicline was administered prior to placement in a locomotor activity chamber to determine whether varenicline influenced baseline locomotor activity. To determine the effect of nicotinic modulation on ethanol-induced motor incoordination, varenicline was administered 30 minutes prior to an acute ethanol injection and then mice were tested on the balance beam, dowel test, or fixed-speed rotarod. To examine ethanol’s sedative-hypnotic effects, varenicline was administered 30 minutes prior to 4 g/kg ethanol and the duration of loss of righting reflex (LORR) was measured.
Results: Varenicline markedly reduced baseline locomotor activity in C57BL/6J mice. Varenicline increased ethanol-induced ataxia when measured on the balance beam and dowel test but had no effect when measured on the fixed-speed rotarod. Pretreatment with varenicline increased the duration of LORR.
Conclusions: These data provide evidence that nAChRs may be involved in the ataxic and sedative effects of ethanol. It is possible that one mechanism that could contribute to the ability of varenicline to decrease ethanol consumption may be through increasing negative behavioral effects of alcohol.