Abstract
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 β2* 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 α7* nAChRs) with dihydro-β-erythroidine (a more selective antagonist of β2* 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 β2−/− mice but not in β2+/+ or wild-type mice.
Conclusions
These data indicate that inhibition of both α7* and β2* nAChRs is necessary to prevent development of sensitization of cocaine-elicited increases in extracellular dopamine levels in the ventral striatum of mice.
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Acknowledgements
We thank Marco Savigni and Delphine Houtteman for skillful technical assistance. This work was supported by grants from the Italian MIUR (MM05152538) (M.Z.) and grants #DA00436, DA14241 and AA15632 from the National Institutes of Health (M. R. P.). AdeKD’E is Research Associate from Fonds National de la Recherche Scientifique (Belgium). The Authors have no financial interest in or financial conflict with the subject matter or the materials discussed in the manuscript.
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Zanetti, L., de Kerchove D’Exaerde, A., Zanardi, A. et al. Inhibition of both α7* and β2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum. Psychopharmacology 187, 181–188 (2006). https://doi.org/10.1007/s00213-006-0419-y
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DOI: https://doi.org/10.1007/s00213-006-0419-y