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

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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
Issue number8
Publication statusPublished - 15 Apr 2002


  • Amphetamine
  • Amphetamine-Related Disorders
  • Animals
  • Association Learning
  • Behavior, Animal
  • Central Nervous System Stimulants
  • Cocaine
  • Cocaine-Related Disorders
  • Dopamine
  • Dopamine Uptake Inhibitors
  • In Vitro Techniques
  • Journal Article
  • Male
  • Mecamylamine
  • Motivation
  • Motor Activity
  • Neuronal Plasticity
  • Neurons
  • Nicotine
  • Nicotinic Antagonists
  • Nucleus Accumbens
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic

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