title: Psychostimulant-induced behavioral sensitization depends on nicotinic receptor activation.
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.
authors.affiliation: Drug Abuse Program, Research Institute Neurosciences Vrije Universiteit, Department of Medical Pharmacology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, The Netherlands. anm.schoffelmeer.pharm@med.vu.nl
authors.forename: Anton N M
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: Taco J
authors.initials: TJ
authors.lastname: De Vries
authors.forename: George
authors.initials: G
authors.lastname: Wardeh
authors.forename: Henrica W M
authors.initials: HW
authors.lastname: van de Ven
authors.forename: Louk J M J
authors.initials: LJ
authors.lastname: Vanderschuren
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D019969:Amphetamine-Related Disorders / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine