Behavioral and dopaminergic sensitization by nicotine The aim of the following experiments is to determine how neuronal systems in brain are affected by chronic exposure to nicotine and to assess whether these effects can subsequently impact behaviors directed 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 proposed experiments will focus on this neurotransmitter known to be critical for the generation of appetitive behaviors such as locomotion and drug self-administration. Rats, like humans, will work to obtain nicotine. In addition, nicotine use is most often characterized by habitual, repeated intake over long periods of time. It is necessary therefore to gain a better understanding of the short- and long-term changes that are produced by prolonged exposure to the drug. This latter point is important 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 drug seeking behaviors of prolonged exposure to the drug either actively or passively. The following experiments will seek to elucidate these consequences by studying stimulant-induced locomotion, midbrain DA activation and self-administration in rats. Experiments in Aim 1 will characterize the effects of different nicotine exposure regimens on the induction of sensitization by nicotine. Those in Aim 2 will seek to identify the brain regions containing the nicotine acetylcholine receptor fields underlying the induction of sensitization. Finally, the impact of nicotine sensitization 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 of nicotine and the manner in which prolonged exposure to the drug may exacerbate drug-directed behaviors.
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