The present application is a request for continued funding of a project entitled """"""""Cocaine Discrimination in Humans: Pharmacological Specificity"""""""" (DA010325). Recent data indicate that nearly 2 million Americans used cocaine in the past month. Alarmingly, between 1991 and 2001 the number of 8th, 10th, and 12th graders that reported using cocaine in the past 30 days increased 140, 86, and 50 percent, respectively. Thus, cocaine abuse continues to represent a significant public health concern, and will likely remain a problem for the foreseeable future. Intensive research efforts have been aimed at elucidating the neuropharmacological mechanisms that mediate the effects of cocaine. Drug-discrimination studies with laboratory animals that used the substitution and pretreatment methodologies have implicated a prominent role of dopamine in mediating the effects of cocaine. During the initial funding period of this project we used a drug discrimination task and the substitution methodology to demonstrate that dopamine systems are involved in mediating the discriminative-stimulus effects of cocaine in humans. We are not aware of any published studies in which the discriminative-stimulus effects of cocaine were assessed in humans following pretreatment with another drug even though drug-discrimination procedures may be particularly well suited for studying agonist-antagonist interactions.
The aim of this application is to further characterize the role of dopamine in mediating the discriminative-stimulus effects of cocaine in humans using a pretreatment methodology. To accomplish this aim, 3 laboratory experiments will be conducted with volunteers with histories of cocaine abuse. The discriminative-stimulus and subjective effects of cocaine will be assessed alone and following pretreatment with mazindol, a dopamine uptake blocker (Exp. 1); fluphenazine, a D1-D2 dopamine receptor antagonist (Exp. 2); and haloperidol, a D2 dopamine receptor antagonist (Exp. 3). We predict that pretreating volunteers with a dopamine agonist or antagonist will shift the cocaine dose-response curve, leftward and rightward, respectively. The experiments proposed in this """"""""proof-of-concept"""""""" continuation application will provide additional information concerning the role of dopamine in mediating the discriminative-stimulus effects of cocaine in humans. Elucidating the role of dopamine in mediating the effects of cocaine may guide the development of pharmacological interventions for cocaine.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA010325-07
Application #
6571817
Study Section
Special Emphasis Panel (ZRG1-BBBP-1 (01))
Program Officer
Lynch, Minda
Project Start
1997-03-01
Project End
2007-06-30
Budget Start
2003-08-01
Budget End
2004-06-30
Support Year
7
Fiscal Year
2003
Total Cost
$219,000
Indirect Cost
Name
University of Kentucky
Department
Psychology
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Reynolds, Anna R; Bolin, B Levi; Stoops, William W et al. (2013) Relationship between drug discrimination and ratings of subjective effects: implications for assessing and understanding the abuse potential of D-amphetamine in humans. Behav Pharmacol 24:523-32
Bolin, B Levi; Reynolds, Anna R; Stoops, William W et al. (2013) Relationship between oral D-amphetamine self-administration and ratings of subjective effects: do subjective-effects ratings correspond with a progressive-ratio measure of drug-taking behavior? Behav Pharmacol 24:533-42
Stanley, Matthew D; Poole, Mégan M; Stoops, William W et al. (2011) Amphetamine self-administration in light and moderate drinkers. Alcohol Clin Exp Res 35:443-53
Vansickel, Andrea R; Stoops, William W; Rush, Craig R (2010) Human sex differences in d-amphetamine self-administration. Addiction 105:727-31
Sevak, Rajkumar J; Stoops, William W; Rush, Craig R (2010) Behavioral effects of d-amphetamine in humans: influence of subclinical levels of inattention and hyperactivity. Am J Drug Alcohol Abuse 36:220-7
Vansickel, Andrea R; Poole, Megan M; Stoops, William W et al. (2009) Stimulant-induced changes in smoking and caloric intake: influence of rate of onset. Pharmacol Biochem Behav 92:597-602
Vansickel, Andrea R; Lile, Joshua A; Stoops, William W et al. (2007) Similar discriminative-stimulus effects of D-amphetamine in women and men. Pharmacol Biochem Behav 87:289-96
Vansickel, Andrea R; Stoops, William W; Glaser, Paul E A et al. (2007) A pharmacological analysis of stimulant-induced increases in smoking. Psychopharmacology (Berl) 193:305-13
Stoops, William W; Lile, Joshua A; Glaser, Paul E A et al. (2006) A low dose of aripiprazole attenuates the subject-rated effects of d-amphetamine. Drug Alcohol Depend 84:206-9
Stoops, William W (2006) Aripiprazole as a potential pharmacotherapy for stimulant dependence: human laboratory studies with d-amphetamine. Exp Clin Psychopharmacol 14:413-21

Showing the most recent 10 out of 26 publications