Role of different nicotinic acetylcholine receptors in mediating behavioral and neurochemical effects of ethanol in mice.
Ethanol and nicotine are the most abused drugs, and it is well known that co-abuse of ethanol and nicotine is frequent in human beings. We have previously obtained results indicating that the ethanol-induced stimulation of both the mesolimbic dopamine system and locomotor activity may involve activation of central nicotinic acetylcholine receptors (nAChRs), especially those located in the ventral tegmental area. Different subpopulations of nAChRs have been identified, and, in the present series of experiments, we have studied the effects of various nAChR antagonists on the stimulation of dopamine overflow in the nucleus accumbens and on locomotor activity induced by ethanol in male mice. Ethanol (2.0 g/kg, i.p.) enhanced dopamine overflow in the nucleus accumbens by approximately 40%, measured by means of in vivo microdialysis in awake, freely moving mice. Mecamylamine (negative allosteric modulator of nAChR; 2.0 mg/kg, i.p.) blocked the ethanol-induced stimulation of both locomotor activity and accumbal dopamine overflow. Methyllycaconitine citrate (alpha(7) antagonist; 2.0 mg/kg, i.p.) and dihydro-beta-erythroidine (competitive and selective alpha(4)beta(2) antagonist; 0.5 mg/kg, s.c.), in doses that had no marked effects per se, did not significantly reduce the behavioral and neurochemical stimulation caused by ethanol. The present results support the suggestion that the stimulatory effects of ethanol on locomotor activity and dopamine release do not involve the alpha(4)beta(2) or alpha(7) subunit compositions of the nAChR and that the effects of mecamylamine are mediated through a site not directly associated with the alpha(4)beta(2) or alpha(7) nAChR subunits.
Larsson
Anna
A
Institute of Physiology and Pharmacology, Department of Pharmacology, Göteborg University, Box 431, SE-405 30, Göteborg, Sweden.
Svensson
Lennart
L
Söderpalm
Bo
B
Engel
Jörgen A
JA
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000502:physiology*
D011978:Receptors, Nicotinic; D000431:Ethanol; D004298:Dopamine