This proposal focuses on evaluation of the reinforcing effects of two classes of drug. One is the benzodiazepine (BZ) ligands that act on BZ receptors or on a subtype of these receptors, either as high or low efficacy agonists. The second class is defined both chemically and pharmacologically. Chemically, these drugs are phenylisopropylamine derivatives. Pharmacologically, they are either stimulants such as amphetamine, entactogens such as MDMA and MDA, or hallucinogens such as DOM Also, current projects evaluating the reinforcing effects of stimulant and depressant drugs that are submitted by industry, academia, and governmental agencies will continue. The procedures to study these compounds involve their contingent intravenous administration by rhesus monkeys under an FR10 TO 10"""""""" schedule of drug delivery. The baseline drug is 0.1 mg/kg methohexital, and the test compounds will be substituted on this baseline. In particularly interesting cases, i.e., if a low efficacy BZ agonist maintains similar rates of responding as a higher efficacy BZ agonist, the FR contingency will be increased systematically to determine if the biochemically- determined differences in efficacy are reflected in a different capacity to maintain responding in the face of increased FR requirements. in addition to this evaluation, this project will initiate studies that are designed to determine whether the endocrinological responses to drugs of abuse are the same in animals that actively self-administer drugs as is those that receive the same doses by passive administration. For this research, pairs of rhesus monkeys will be yoked in experiments in which the drug self-administered by one animal is received as well by its partner. Blood will be drawn from both animals through the indwelling catheters at appropriate times during this study and analyzed by Dr. Cicero for endocrinological changes. The roles of the animals will be switched -- the passive monkey becomes active and vice versa -- and the importance of control of the administration of the drug should be ascertained.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA009161-03
Application #
2749094
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Wetherington, Cora Lee
Project Start
1996-09-01
Project End
1999-07-31
Budget Start
1998-09-01
Budget End
1999-07-31
Support Year
3
Fiscal Year
1998
Total Cost
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
Reilly, Mark P; Berndt, Sonja I; Woods, James H (2016) On the nature of directed behavior to drug-associated light cues in rhesus monkeys (Macaca mulatta). Behav Anal (Wash D C) 16:200-209
Fantegrossi, W E; Ciullo, J R; Wakabayashi, K T et al. (2008) A comparison of the physiological, behavioral, neurochemical and microglial effects of methamphetamine and 3,4-methylenedioxymethamphetamine in the mouse. Neuroscience 151:533-43
Fantegrossi, William E (2007) Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity? Psychopharmacology (Berl) 189:471-82
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
Collins, Gregory T; Witkin, Jeffrey M; Newman, Amy H et al. (2005) Dopamine agonist-induced yawning in rats: a dopamine D3 receptor-mediated behavior. J Pharmacol Exp Ther 314:310-9
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, William E; Kiessel, Christina L; De la Garza 2nd, Richard et al. (2005) Serotonin synthesis inhibition reveals distinct mechanisms of action for MDMA and its enantiomers in the mouse. Psychopharmacology (Berl) 181:529-36
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
Galuska, Chad M; Woods, James H (2005) Acquisition of cocaine self-administration with unsignaled delayed reinforcement in rhesus monkeys. J Exp Anal Behav 84:269-80
Broadbear, Jillian H; Winger, Gail; Woods, James H (2004) Self-administration of fentanyl, cocaine and ketamine: effects on the pituitary-adrenal axis in rhesus monkeys. Psychopharmacology (Berl) 176:398-406

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