Enhanced Nicotinic Receptor Function and Drug Abuse Vulnerability.
From: Committee on Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Aug 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 33
- Pages: 8771-8
- Medium: Internet
- Language: English
- Citation (JAMA): Fagen Zara M, Mitchum Robert, Vezina Paul, et al. Enhanced Nicotinic Receptor Function and Drug Abuse Vulnerability.. J. Neurosci. Aug 2007;27:8771-8
Abstract
In animals and humans, vulnerability to drug abuse varies among individuals. Animals that display high activity levels in a novel environment are more likely to self-administer psychostimulant drugs, including nicotine, cocaine, amphetamine, and morphine. Recent reports from behavioral studies indicate that nicotinic acetylcholine receptor (nAChR) activity contributes to the rewarding effects of several different addictive drugs. Thus, we hypothesized that differences in nAChR activity may contribute to the predisposition to drug self-administration. After screening of adult rats (>60 d postnatal) for the behavioral response to a novel environment, electrophysiological measures of nAChR function were conducted in brain slices that included the mesoaccumbens dopamine neurons of the ventral tegmental area (VTA). We found a positive correlation between the response to novelty and nAChR function in each assay conducted, including nAChR modulation of glutamatergic and GABAergic synaptic inputs to VTA dopamine neurons, as well as somatic nAChR responses of VTA neurons. The response to novelty and sensitivity to addictive drugs are positively correlated with the hormonal response to stress. Consistent with this observation, we found enhanced nAChR responses in vitro after a 48 h corticosterone treatment and in vivo after 48 h of repeated stress. Each of these effects was inhibited by RU486 (11beta-[p-(dimethylamino)phenyl]-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one) pretreatment, suggesting a steroid hormone receptor-dependent process. These findings suggest that differences in nAChR function within the mesoaccumbens dopamine system may contribute to individual differences in drug abuse vulnerability and that these are likely attributable to differences in stress hormone levels.
Mesh Headings (Keywords): Animals, Behavior, Animal, Bicuculline, Cells, Cultured, Corticosterone, Dopamine, Electric Stimulation, Hormone Antagonists, Male, Membrane Potentials, Mifepristone, Motor Activity, Neurons, Nicotine, Nicotinic Agonists, Patch-Clamp Techniques, Rats, Rats, Sprague-Dawley, Receptors, Nicotinic, Statistics as Topic, Stress, Ventral Tegmental Area
Check for Full Text / PubMed Unique Identifier (PMID): 17699659
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