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A role for neuronal nicotinic acetylcholine receptors in ethanol-induced stimulation, but not cocaine- or methamphetamine-induced stimulation

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Abstract

Rationale

Cocaine (COC), ethanol (EtOH), and methamphetamine (MA) are widely abused substances and share the ability to induce behavioral stimulation in mice and humans. Understanding the biological basis of behavioral stimulation to COC, EtOH, and MA may provide a greater understanding of drug and alcohol abuse.

Objectives

In these studies we set out to determine if neuronal nicotinic acetylcholine receptors were involved in the acute locomotor responses to these drugs, our measure of behavioral stimulation.

Methods

A panel of acetylcholine receptor antagonists was used to determine if nicotinic receptors were involved in EtOH- and psychostimulant-induced stimulation. We tested the effect of these drugs in genotypes of mice (FAST and DBA/2J) that are extremely sensitive to this drug effect. To determine which acetylcholine receptor subunits may be involved in this response, relative expression of the α3, α6, β2, and β4 subunit genes was examined in mice selectively bred for high and low response to EtOH.

Results

Mecamylamine, but not hexamethonium, attenuated the acute locomotor response to EtOH. The acetylcholine receptor antagonist dihydro-β-erythroidine and methyllycaconitine had no effect on this response. The α6 and β4, but not α3 or β2, subunits of the acetylcholine receptor were differentially expressed between mice bred for extreme differences in EtOH stimulation. Mecamylamine had no effect on psychostimulant-induced locomotor activity.

Conclusions

Neuronal nicotinic receptors are involved in EtOH, but not psychostimulant, stimulation. These studies suggest a lack of involvement of some nicotinic receptor subtypes, but more work is needed to determine the specific receptor subtypes involved in this behavior.

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Acknowledgements

These studies were performed with support from P60 AA10760 (TJP), P50 DA018165 (TJP), F31 AA015822 (HMK), the N.L. Tartar Research Fund (HMK), and the Department of Veterans Affairs (TJP). The authors would like to thank Dr. Kristine Wiren for use of her laboratory equipment for the qRT-PCR study and Joel Hashimoto, Carrie McKinnon, Na Li, and Sue Burkhart-Kasch for technical assistance with these experiments.

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Authors and Affiliations

  1. Department of Behavioral Neuroscience, Portland Alcohol Research Center, Methamphetamine Abuse Research Center, Oregon Health & Science University and VA Medical Center, Portland, OR, 97239, USA

    Helen M. Kamens & Tamara J. Phillips

  2. VA Medical Center Research Service, R&D 32, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA

    Tamara J. Phillips

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  1. Helen M. Kamens
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  2. Tamara J. Phillips
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Correspondence to Tamara J. Phillips.

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Kamens, H.M., Phillips, T.J. A role for neuronal nicotinic acetylcholine receptors in ethanol-induced stimulation, but not cocaine- or methamphetamine-induced stimulation. Psychopharmacology 196, 377–387 (2008). https://doi.org/10.1007/s00213-007-0969-7

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  • DOI: https://doi.org/10.1007/s00213-007-0969-7

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