Behavioral and dopaminergic sensitization by nicotine The aim of the following experiments is to determine how neuronal systems in brain are affected bychronic exposure to nicotine and to assess whether these effects can subsequently impact behaviorsdirected at obtaining the drug. Because nicotine, like other stimulants self-administered by rats and humans,is known to promote neurotransmission in the ascending midbrain dopamine (DA) systems, the proposedexperiments will focus on this neurotransmitter known to be critical for the generation of appetitive behaviorssuch as locomotion and drug self-administration. Rats, like humans, will work to obtain nicotine. In addition, nicotine use is most often characterized byhabitual, repeated intake over long periods of time. It is necessary therefore to gain a better understanding ofthe short- and long-term changes that are produced by prolonged exposure to the drug. This latter point isimportant because, while knowledge of the acute effects of nicotine on brain has increased somewhat,relatively little is known of the consequences for midbrain DA neurotransmission and the promotion of drugseeking behaviors of prolonged exposure to the drug either actively or passively. The following experimentswill seek to elucidate these consequences by studying stimulant-induced locomotion, midbrain DA activationand self-administration in rats. Experiments in Aim 1 will characterize the effects of different nicotine exposure regimens on theinduction of sensitization by nicotine. Those in Aim 2 will seek to identify the brain regions containing thenicotine acetylcholine receptor fields underlying the induction of sensitization. Finally, the impact of nicotinesensitization on the motivation to self-administer nicotine will be assessed in Aim 3. The results obtained will lead to a better understanding of the mechanisms underlying the pursuit ofnicotine and the manner in which prolonged exposure to the drug may exacerbate drug-directed behaviors.
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