The revised application is entitled """"""""Human Cocaine Discrimination: Pharmacological Specificity"""""""". The title was changed since less emphasis is given to elucidating the neuropharmacological mechanisms underlying the discriminative stimulus effects of cocaine in human research volunteers. The revised application consists of 5 inpatient, laboratory experiments aimed at characterizing the discriminative stimulus effects of cocaine in humans. Exp. 1 will replicate the only other study that established cocaine as a discriminative stimulus in humans, and extend these findings by testing the discriminative stimulus effects of d- amphetamine and pentobarbital to further determine the pharmacological specificity of the cocaine-placebo discrimination. Exp. 2 will determine the effects of training dose on subsequent discrimination performance. Exp. 3-5 will test the discriminative stimulus effects of 6 compounds (i.e., mazindol, methylphenidate, bupropion, diethylpropion, desipramine and fluoxetine) in cocaine-trained humans. d-Amphetamine and pentobarbital will be included as a positive and negative control, respectively, in each of these experiments. Two training conditions will be used in each experiment to further explore the influence of cocaine training dose on subsequent discrimination performance. Drug-effect and mood questionnaires will be used in each experiment. The experiments proposed in this application have at least 6 important implications. First, these experiments will lay the groundwork for studying the discriminative stimulus effects of cocaine in humans. Second, these experiments will determine the influence of cocaine training dose on subsequent drug discrimination performance. Third, because some of the compounds to be tested exert their effects primarily via dopamine systems (i.e., mazindol, methylphenidate, bupropion, diethylpropion) and others via norepinephrine (i.e., desipramine) or serotonin (i.e., fluoxetine) systems, these experiments will begin to elucidate the neuropharmacological mechanisms underlying the discriminative stimulus effects of cocaine in humans, and whether these mechanisms vary across different training conditions. Fourth, because all of the compounds have previously been tested in nonhuman laboratory animals trained to discriminate between cocaine and vehicle, these experiments will begin to determine, albeit indirectly, to what extent the findings from preclinical studies generalize to humans. Fifth, the inclusion of drug-effect and mood questionnaires will provide ancillary information concerning the relationship between the discriminative stimulus and subjective effects of cocaine. Finally, because the interoceptive and discriminative stimulus effects of cocaine clearly contribute to its abuse, the experiments proposed in this application could provide information relevant to the treatment of cocaine abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA010325-03
Application #
2872080
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Lynch, Minda
Project Start
1997-03-01
Project End
1999-06-30
Budget Start
1999-02-01
Budget End
1999-06-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Mississippi Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
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

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