Nicotine addiction: insights from recent animal studies.
BACKGROUND
Recent preclinical behavioral and neurobiological research has characterized important behavioral features and has identified neurobiological substrates that may underlie nicotine reinforcement and addiction.


OBJECTIVE
To examine recent advances on nicotine exposure in preclinical models, from three perspectives: (a) the chronopharmacokinetics of nicotine, (b) behavioral studies on nicotine reinforcement, withdrawal, and reinstatement/relapse, and (c) effects of nicotine on neurobiological substrates after repeated exposure.


RESULTS
Preclinical studies can be used to operationally model selected aspects of nicotine reinforcement, withdrawal, and reinstatement or relapse. These may be used to investigate the functional in vivo consequences of acute and long-term changes in neuronal acetylcholine receptor populations that follow nicotine exposure. Behavioral studies focusing on distinct stages of nicotine exposure (e.g., active reinforcement vs. cessation or reinstatement) may also be used in parallel with studies on dopaminergic function, a proposed substrate for the reinforcing effects of nicotine, and of opioid receptor function, a possible site of neuroadaptations secondary to nicotine exposure.


CONCLUSIONS
While no single current animal model may capture the experience of human smoking or nicotine addiction, increasingly, separate animal models are capturing the full spectrum of behavioral and neurobiological dimensions of this complex condition.
Rockefeller University, Laboratory on the Biology of Addictive Diseases, Box 171, 1230 York Avenue, New York, NY 10021-6399, USA.
A M
AM
Mathieu-Kia
S H
SH
Kellogg
E R
ER
Butelman
M J
MJ
Kreek
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm; D004298:Dopamine / Q000378:metabolism; D005731:Ganglionic Stimulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D008032:Limbic System / Q000378:metabolism; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism; D009538:Nicotine / Q000493:pharmacokinetics / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D012054:Reinforcement, Psychology; D012907:Smoking / Q000378:metabolism / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000523:psychology; D019966:Substance-Related Disorders / Q000235:genetics / Q000378:metabolism / Q000523:psychology
D005731:Ganglionic Stimulants; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D011957:Receptors, Opioid; D009538:Nicotine; D004298:Dopamine