The mesolimbic dopamine system mediates the reinforcing effects of nicotine and other drugs of abuse. Thus the genes affecting the functionality of the mesolimbic dopamine system can be contributing factors to predisposition to nicotine abuse. These genes include dopamine receptors, signaling molecules of cAMP pathway such as adenylate cyclase, and others. Evidence put forth by a number of investigators suggests that the difference in the different biochemical profile of cAMP pathway in the mesolimbic dopamine system may result in differential predilection to abused drugs. The precise relation of up-regulated cAMP signaling pathway~y and nicotine predilection, however, remains vague. The present study seeks to bridge this gap by investigating the consequence of up-regulated cAMP pathway in transgenic mice, caused by a subtle substitution mutation in the dopamine D2 receptor, on nicotine responsiveness. Particularly, these studies seek to produce a strain of transgenic mice that express the mutant D2 receptor and to investigate whether the mutant D2 receptor will result in up-regulation of cAMP pathway in transgenic mice and therefore increased vulnerability to nicotine abusing. The availability of transgenic mice expressing the mutant D2 receptor will help establish the causal effect relationship of an up- regulated cAMP pathway and predilection to nicotine abuse. The proposed studies will also lead to an understanding of whether a subtle change in structure of dopamine D2 receptor, one of mediators for the basic neurobiological function of mesolimbic dopamine system, may affect predisposition to nicotine abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA013332-02
Application #
6349046
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2000-09-01
Project End
2001-08-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2000
Total Cost
$172,711
Indirect Cost
Name
University of California Irvine
Department
Type
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Henry, Shayna L; Jamner, Larry D; Whalen, Carol K (2012) I (should) need a cigarette: adolescent social anxiety and cigarette smoking. Ann Behav Med 43:383-93
Butler, Jorie M; Whalen, Carol K; Jamner, Larry D (2009) Bummed out now, feeling sick later: weekday versus weekend negative affect and physical symptom reports in high school freshmen. J Adolesc Health 44:452-7
Gray, Barbara (2008) Enhancing transdisciplinary research through collaborative leadership. Am J Prev Med 35:S124-32
Ahmad, Sajjad; Franz, Gregor A (2008) Raising taxes to reduce smoking prevalence in the US: a simulation of the anticipated health and economic impacts. Public Health 122:3-10
Gehricke, Jean-G; Loughlin, Sandra E; Whalen, Carol K et al. (2007) Smoking to self-medicate attentional and emotional dysfunctions. Nicotine Tob Res 9 Suppl 4:S523-36
Ahmad, Sajjad; Billimek, John (2007) Limiting youth access to tobacco: comparing the long-term health impacts of increasing cigarette excise taxes and raising the legal smoking age to 21 in the United States. Health Policy 80:378-91
Park, Minjung K; Belluzzi, James D; Han, Sun-Ho et al. (2007) Age, sex and early environment contribute to individual differences in nicotine/acetaldehyde-induced behavioral and endocrine responses in rats. Pharmacol Biochem Behav 86:297-305
Loughlin, Sandra E; Islas, Michelle I; Cheng, Michelle Y et al. (2006) Nicotine modulation of stress-related peptide neurons. J Comp Neurol 497:575-88
Stokols, Daniel (2006) Toward a science of transdisciplinary action research. Am J Community Psychol 38:63-77
Villegier, Anne-Sophie; Salomon, Lucas; Granon, Sylvie et al. (2006) Monoamine oxidase inhibitors allow locomotor and rewarding responses to nicotine. Neuropsychopharmacology 31:1704-13

Showing the most recent 10 out of 40 publications