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


OBJECTIVE
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 alpha3, alpha6, beta2, and beta4 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-beta-erythroidine and methyllycaconitine had no effect on this response. The alpha6 and beta4, but not alpha3 or beta2, 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.
Kamens
Helen M
HM
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
Phillips
Tamara J
TJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D021122:Protein Subunits; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D000431:Ethanol; D008694:Methamphetamine; D003042:Cocaine