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Inhibition of both alpha7* and beta2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum.

par Zanetti, Lara;de Kerchove d'Exaerde, Alban ;Zanardi, Alessio;Changeux, J.-P.;Picciotto, Marina R;Zoli, M
Référence Psychopharmacologia, 187, 2, page (181-188)
Publication Publié, 2006-08

Article révisé par les pairs

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Résumé :

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 beta2* 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 alpha7* nAChRs) with dihydro-beta-erythroidine (a more selective antagonist of beta2* 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 beta2-/- mice but not in beta2+/+ or wild-type mice. CONCLUSIONS: These data indicate that inhibition of both alpha7* and beta2* nAChRs is necessary to prevent development of sensitization of cocaine-elicited increases in extracellular dopamine levels in the ventral striatum of mice.