Reinforcement from most drugs, including nicotine, depends largely on their interoceptive stimulus effects. Although traditional subjective measures may help, clearer understanding of these effects, and factors that influence them, requires use of behavioral drug discrimination procedures. Knowledge of the discriminative stimulus effects of nicotine may be critical in understanding its dependence potential and in evaluating new treatments for nicotine dependence. In the first 2.5 years of this project, we have established a procedure for assessing nicotine discrimination I humans using a measured-dose nasal spray delivery system and have begun to examine factors influencing this discrimination, such as between-subjects differences (e.g.. Sex, smoking status) and within-subjects factors (e.g. training conditions). The research proposed in the present application directly extends this line of investigation to key questions concerning the relationship between nicotine discrimination and reinforcement, mechanisms underlying nicotine discrimination, and common environmental factors which may, acutely influence nicotine discrimination. More specifically, we plan to: 1) identify the lowest reliably discriminable nicotine doses (discrimination threshold) in smokers and nonsmokers; 2) compare effects of central plus peripheral nicotine blockage (via mecamylamine) with effects of peripheral blockade only (via trimethaphan) to verify that nicotine discrimination is dependent on its central effects; 3) systematically evaluate alterations in the discriminative stimulus effects of nicotine due to situational conditions that commonly accompany nicotine intake via smoking in the natural environment, including concurrent drug consumption (alcohol, caffeine) and concurrent engagement in light physical activity; and 4) determine the relationship between nicotine choice (a measure of reinforcement) and nicotine discrimination following each of these manipulations. Findings from the first study may assist efforts to identify thresholds for nicotine reinforcement and development of dependence, an objective with important implications for prevention and treatment of nicotine dependence. Results of this program may also ultimately assist in the development of new treatments for smoking cessation by: providing a means for testing new medications to alter nicotine's reinforcing effects; confirming that these effects are centrally-mediated; and by determining the influence of situational factors of these effects, thus providing a better understanding of how these factors may impact on nicotine reinforcement, maintenance of smoking, and smoking relapse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA008578-04A1
Application #
2398799
Study Section
Special Emphasis Panel (ZDA1-KXA-N (17))
Program Officer
Aigner, Thomas G
Project Start
1994-01-01
Project End
2002-06-30
Budget Start
1997-08-05
Budget End
1998-06-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Perkins, Kenneth A (2009) Discriminative stimulus effects of nicotine in humans. Handb Exp Pharmacol :369-400
Perkins, Kenneth A; Lerman, Caryn; Coddington, Sarah et al. (2008) Gene and gene by sex associations with initial sensitivity to nicotine in nonsmokers. Behav Pharmacol 19:630-40
Perkins, Kenneth A; Fonte, Carolyn; Stolinski, Amy et al. (2005) The influence of caffeine on nicotine's discriminative stimulus, subjective, and reinforcing effects. Exp Clin Psychopharmacol 13:275-81
Perkins, Kenneth A; Fonte, Carolyn; Blakesley-Ball, Richard et al. (2005) The discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine as a function of light physical activity. Nicotine Tob Res 7:791-800
Perkins, Kenneth A; Jetton, Chris; Stolinski, Amy et al. (2003) The consistency of acute responses to nicotine in humans. Nicotine Tob Res 5:877-84
Perkins, K A; Fonte, C; Sanders, M et al. (2001) Threshold doses for nicotine discrimination in smokers and non-smokers. Psychopharmacology (Berl) 155:163-70
Perkins, K A; Fonte, C; Ashcom, J et al. (2001) Subjective responses to nicotine in smokers may be associated with responses to caffeine and to alcohol. Exp Clin Psychopharmacol 9:91-100
Perkins, K A; Fonte, C; Meeker, J et al. (2001) The discriminative stimulus and reinforcing effects of nicotine in humans following nicotine pretreatment. Behav Pharmacol 12:35-44
Perkins, K A; Gerlach, D; Vender, J et al. (2001) Sex differences in the subjective and reinforcing effects of visual and olfactory cigarette smoke stimuli. Nicotine Tob Res 3:141-50
Perkins, K A; Fonte, C; Grobe, J E (2000) Sex differences in the acute effects of cigarette smoking on the reinforcing value of alcohol. Behav Pharmacol 11:63-70

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