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Nicotine self-administration in an animal model

Institution: Scripps Research Institute
Investigator(s): George Koob, Ph.D.
Award Cycle: 2003 (Cycle 12) Grant #: 12RT-0099 Award: $660,156
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Introduction and Objective: Tobacco addiction is a major health problem in the United States and the world with estimates of over 47 million current American smokers. Tobacco smoking is the leading, avoidable cause of disease and premature death in the U.S. It is estimated that more than 430,000 smoking-related deaths occur annually in the United States, and the economic costs are substantial, totaling over $138 billion in 1995. A critical question in the neurobiology of dependence on nicotine is what conveys the vulnerability to use tobacco products and the vulnerability to the transition from tobacco use to dependence. However this question is difficult to approach given that there are few animal models available to explore the transition from tobacco use to tobacco dependence from a motivational perspective.

Progress: Work from the first funding period characterized our model of unlimited access nicotine self-administration using 23-hour access to the drug and the transition to a dependent state. Dose-dependent alterations in the pattern nicotine self-administration, extinction of nicotine-seeking behavior, dependence measures, and changes in the pattern of responding for food and water are being characterized. Subsequent studies demonstrating that rats challenged with the nicotinic antagonist mecamylamine exhibit changes in nicotine intake have begun to validate our model.

Impact: Work from this funding period has provided us with a reliable dependence model and new avenues of research that will serve as exciting resources for exploring in future studies the neurobiological changes that convey vulnerability to the development of dependence in certain individuals.
Publications

Neurobiological mechanisms in the transition from drug use to drug dependence.
Periodical: Neuroscience Biobehavior Index Medicus:
Authors: Koob GF, Ahmed SH, Boutrel B, Chen SA, Kenny PJ, Markou A, O'Dell LE, et al. ART
Yr: 2004 Vol: 27 Nbr: Abs: Pg: 739-749

Nicotine withdrawal in adolescent and adult rats.
Periodical: Annals of the New York Academy of Sciences Index Medicus:
Authors: O'Dell LE, Bruijnzeel AW, Ghozland S, Markou A, Koob GF ART
Yr: 0 Vol: Nbr: Abs: Pg:

Characterization of nicotine intake, extinction, and precipitated withdrawal using 23-hr access to nicotine self-administration in rats.
Periodical: TRDRP Annual Report to the State of California Legislature Index Medicus:
Authors: O'Dell LE, Chen SA, Paterson NE, Markou A, Balster RL, Koob GF ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Adolescent rats are less susceptible to nicotine withdrawal signs relative to their adult counterparts.
Periodical: College on Problems of Drug Dependence Index Medicus:
Authors: O'Dell LE, Bruijnzeel AW, Markou A, Koob GF ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Metabotropic Glutamate 5 receptor antagonist MPEP decreased nicotine and cocaine self -administration but not nicotine and cocaine-induced facilitation of brain reward function in rats
Periodical: Annals of the New York Academy of Sciences Index Medicus:
Authors: Kenny, P.J., Paterson N.E., Boutrel B, Semenova S., Harrison A.A., Gasparini, F. , Koob G. ART
Yr: 2003 Vol: Nbr: Abs: Pg: 415-418

Nicotine withdrawal in adolescent and adult rats
Periodical: Annals of the New York Academy of Sciences Index Medicus:
Authors: O'dell, L.E. Bruijnzee;, AW., Ghozland ,S. Markou, A and Koob, G.F. ART
Yr: 2004 Vol: Nbr: Abs: Pg: 167-174

Investigations using immunization to attenuate the psychoactive effects of nicotine
Periodical: Bioorganic Medical Chemistry Index Medicus:
Authors: Carrera, M.R.A. , Ashley, J. A., Hoffman , T. Z., Isomura S., Wirsching, P. Koob, G.F. ART
Yr: 2004 Vol: Nbr: Abs: Pg: 563-570

Monoamine Oxidase inhibition dramatically increases the motivation to self-administer nicotine in rats
Periodical: Journal of Neuroscience Index Medicus:
Authors: Guillem K, Vouillac C., Azar, MR., Parsons., L.H., Koob, G.F. Cador , M. and Stinus ART
Yr: 2005 Vol: Nbr: Abs: Pg: 8593-8600

Diminished nicotine withdrawal in adolescent rats implications for vulnerability to addicition
Periodical: Psychopharmacology Index Medicus:
Authors: O'Dell, L.E., Bruijnzeel, A.W., Smith R.T., Parsons, L.H. Merves, M.L., Koob G.F. ART
Yr: 2006 Vol: 186 Nbr: Abs: Pg: 612-619

MAO-A and MAO-B inhibition on nicotine self -administration in rats
Periodical: European Journal of Neuroscience Index Medicus:
Authors: Guillem, K., Vouillac, C., Azar, M.R. , Parsons , L.H., Koob, G.F., ART
Yr: 0 Vol: Nbr: Abs: Pg: