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.
|Anno di pubblicazione:||2006|
|Titolo:||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|
|Autore/i:||L. Zanetti; A. DeKerchove D'Exaerde; A. Zanardi; J.P. Changeux; M.R. Picciotto; M. Zoli|
|Codice identificativo ISI:||WOS:000238999000006|
|Codice identificativo Scopus:||2-s2.0-33745751083|
|Tipologia||Articolo su rivista|
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