Prior experiments have shown that primates (rhesus monkeys and baboons) will work for intravenous infusions of racemic MDMA at rates greater than or equal to those produced to obtain cocaine infusions. However, the reinforcing effects of the optical isomers of MDMA have not been previously assessed. Drug discrimination experiments suggest that the complex discriminative stimulus profile of racemic MDMA is attributable to the primarily dopaminergic stimulus effects of (+)-MDMA and the primarily serotonergic stimulus effects of (-)-MDMA. These differential effects of the stereoisomers on neurotransmitter systems have been confirmed in pharmacological studies. The objective of the proposed experiments is to further elucidate the differences between the optical isomers of MDMA by assessing their reinforcing effects in terms of (1) response rate under a fixed ratio schedule and (2) break point under a progressive ratio schedule. Additionally, self-administration data for racemic MDMA will be replicated in the fixed ratio study, and extended by means of a break point analysis in the progressive ratio study. In accord with previous self-administration studies, these behavioral endpoints will be compared with those produced by cocaine and saline, as well as methamphetamine (a drug with a more similar time course to MDMA) and LSD (a drug with more similar neurochemical effects to MDMA). Finally, the relationship between the rewarding and serotonin depleting effects of MDMA will be assessed by pharmacologically challenging self- administration behavior with pre-treatments of various neuroprotective agents.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA005923-03
Application #
6378437
Study Section
Special Emphasis Panel (ZDA1-MXS-M (12))
Program Officer
Babecki, Beth
Project Start
2001-09-30
Project End
Budget Start
2001-09-30
Budget End
2002-06-29
Support Year
3
Fiscal Year
2001
Total Cost
$16,749
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pharmacology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Fantegrossi, W E; Harrington, A W; Kiessel, C L et al. (2006) Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacol Biochem Behav 83:122-9
Fantegrossi, William E; Kugle, Kelly M; Valdes 3rd, Leander J et al. (2005) Kappa-opioid receptor-mediated effects of the plant-derived hallucinogen, salvinorin A, on inverted screen performance in the mouse. Behav Pharmacol 16:627-33
Fantegrossi, W E; Winger, G; Woods, J H et al. (2005) Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys. Drug Alcohol Depend 77:161-8
Fantegrossi, W E; Woods, J H; Winger, G (2004) Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys. Behav Pharmacol 15:149-57