The Journal of Neuroscience, April 15, 2002, 22(8):3269-3276
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, and
Louk J. M. J.
Vanderschuren
Drug Abuse Program, Research Institute Neurosciences
Vrije Universiteit, Department of Medical Pharmacology,
Vrije Universiteit Medical Center, 1081 BT Amsterdam,
The Netherlands
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 [3H]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-
7 subtype
nicotinic receptor antagonist dihydro-
-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.
Key words:
sensitization; nicotine; amphetamine; cocaine; nicotinic
receptors; addiction; learning
Copyright © 2002 Society for Neuroscience 0270-6474/02/2283269-08$05.00/0
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