Rationale: Several studies have suggested that nicotine treatment can modulate the behavioral and neurochemical responses to other psychostimulants, such as cocaine. Objectives: The current study examined the hypothesis that nicotinic acetylcholine receptor (nAChR) blockade influences the ability of cocaine to elicit increases in extracellular dopamine levels. Materials and Methods: Pharmacological studies using nicotinic antagonists as well as genetic inactivation of beta 2* nAChRs were used to determine the effect of nAChR blockade on dopamine levels in ventral striatum elicited by acute or repeated administrations of cocaine in mice. Results: Administration of mecamylamine (a general nicotinic antagonist that is not highly selective for individual nAChR subtypes) or co-administration of methyllycaconitine (a more selective antagonist of alpha 7* nAChRs) with dihydro-beta-erythroidine (a more selective antagonist of beta 2* nAChRs and other heteromeric nAChR subtypes) prevented sensitization of cocaine-elicited increases in extracellular DA levels in the ventral striatum in wild-type mice. In contrast, neither of the more specific antagonists alone was effective in preventing sensitization. Finally, methyllycaconitine administration prevents sensitization in beta 2-/- mice but not in beta 2+/+ or wild-type mice. Conclusions: These data indicate that inhibition of both alpha 7* and beta 2* nAChRs is necessary to prevent development of sensitization of cocaine-elicited increases in extracellular dopamine levels in the ventral striatum of mice.
Inhibition of both alpha 7* and beta 2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum / Zanetti, Lara; A., DeKerchove D'Exaerde; Zanardi, Alessio; J. P., Changeux; M. R., Picciotto; Zoli, Michele. - In: PSYCHOPHARMACOLOGY. - ISSN 0033-3158. - STAMPA. - 187:(2006), pp. 181-188. [10.1007/s00213-006-0419-y]