Psychostimulant-induced behavioral sensitization depends on nicotinic receptor activation

Anton N M Schoffelmeer, Taco J De Vries, George Wardeh, Henrica W M van de Ven, Louk J M J Vanderschuren

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Animal studies have shown that nicotine and psychostimulant drugs (amphetamine and cocaine) share the property of inducing long-lasting behavioral and neurochemical sensitization, which is thought to contribute to their addictive properties. Neuroplasticity subserving learning and memory mechanisms is considered to be involved in psychostimulant-induced sensitization and addiction behavior. Because nicotinic receptors in the brain play a role in the storage of drug-related information underlying reinforcement learning, we evaluated the possibility that activation of central nicotinic receptors may underlie psychostimulant-induced sensitization. Repeated exposure of rats to nicotine profoundly enhanced the psychomotor effects of nicotine and amphetamine 3 weeks after nicotine pretreatment. Moreover, the nicotinic receptor antagonist mecamylamine completely blocked the induction, but not the long-term expression, of behavioral sensitization to amphetamine in amphetamine-pretreated rats. Mecamylamine also prevented the development of cocaine-induced behavioral sensitization. Behavioral sensitization induced by nicotine, amphetamine, or cocaine was associated with an increase in the electrically evoked release of [(3)H]dopamine from nucleus accumbens slices. Coadministration of mecamylamine during pretreatment with nicotine, amphetamine, or cocaine prevented the development of this long-term hyperreactivity of nucleus accumbens dopamine neurons. Similarly, the high-affinity non-alpha7 subtype nicotinic receptor antagonist dihydro-beta-erythroidine prevented the development of amphetamine-induced behavioral and neurochemical sensitization. These data indicate that nicotinic receptor activation (by endogenously released acetylcholine) is a common denominator initiating neuroplasticity involved in the development of amphetamine, as well as cocaine-induced sensitization.

Original languageEnglish
Pages (from-to)3269-76
Number of pages8
JournalJournal of Neuroscience
Volume22
Issue number8
DOIs
Publication statusPublished - 15 Apr 2002

Cite this

Schoffelmeer, A. N. M., De Vries, T. J., Wardeh, G., van de Ven, H. W. M., & Vanderschuren, L. J. M. J. (2002). Psychostimulant-induced behavioral sensitization depends on nicotinic receptor activation. Journal of Neuroscience, 22(8), 3269-76. https://doi.org/20026312