A role for neuronal nicotinic acetylcholine receptors in ethanol-induced stimulation, but not cocaine- or methamphetamine-induced stimulation
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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.
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.
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.
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.
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.
KeywordsMethamphetamine Ethanol Cocaine Stimulation Nicotinic acetylcholine receptors Locomotor activity Selected lines
- Bergstrom HC, Palmer AA, Wood RD, Burkhart-Kasch S, McKinnon CS, Phillips TJ (2003) Reverse selection for differential response to the locomotor stimulant effects of ethanol provides evidence for pleiotropic genetic influence on locomotor response to other drugs of abuse. Alcohol Clin Exp Res 27:1535–1547PubMedCrossRefGoogle Scholar
- Cui C, Booker TK, Allen RS, Grady SR, Whiteaker P, Marks MJ, Salminen O, Tritto T, Butt CM, Allen WR, Stitzel JA, McIntosh JM, Boulter J, Collins AC, Heinemann SF (2003) The beta3 nicotinic receptor subunit: a component of alpha-conotoxin MII-binding nicotinic acetylcholine receptors that modulate dopamine release and related behaviors. J Neurosci 23:11045–11053PubMedGoogle Scholar
- Dick DM, Jones K, Saccone N, Hinrichs A, Wang JC, Goate A, Bierut L, Almasy L, Schuckit M, Hesselbrock V, Tischfield J, Foroud T, Edenberg H, Porjesz B, Begleiter H (2006) Endophenotypes successfully lead to gene identification: results from the collaborative study on the genetics of alcoholism. Behav Genet 36:112–126PubMedCrossRefGoogle Scholar
- Marubio LM, Gardier AM, Durier S, David D, Klink R, Arroyo-Jimenez MM, McIntosh JM, Rossi F, Champtiaux N, Zoli M, Changeux JP (2003) Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors. Eur J Neurosci 17:1329–1337PubMedCrossRefGoogle Scholar
- McClearn GE, Wilson SG, Meredith W (1970) The use of isogenic and heterogenic mouse stocks in behavioral research. In: Thiessen DD (ed) Contributions to behavior-genetic analysis: the mouse as a protoype. Appleton-Century-Crofts, New York, pp 3–22Google Scholar
- National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington, DCGoogle Scholar