The overall aim of this proposal is to continue to attempt to understand more of the factors that lead to and result from abuse of stimulants, depressants, and hallucinogens. 1.
The first aim of this project is a continuation of research that was initiated to determine the effects of cocaine self-administration on blood ACTH and cortisol levels in rhesus monkeys. Self-administered cocaine leads to dose-related increases in these stress hormones, and these increases occurred as well when cocaine was delivered non-contingently. Do these increases occur as well when sedative-hypnotic agents are used to maintain responding. In other words, how general is this finding? 2. The stress hypothesis of drug self-administration suggests that stress, as indicated by increased blood levels of cortisol and ACTH produces increases in the reinforcing effects of drugs. The effects in monkeys of several pre-session stressors on the reinforcing effects of cocaine and other drugs will be measured by changes in progressive ratio performance. The ability of these stressor to increase ACTH and cortisol levels prior to a session, and the effects of the self-administered drugs on these elevated levels will be determined as well. 3. In the rat model of sedative self-administration, the reinforcing effects of a neurosteroid, and other sedative hypnotics will be established, and the ability of picrotoxin, flumazenil, and betaCCE to modify the reinforcing effects of these drugs will be measured. 4.The stress hypothesis of sedative self-administration will be measured in the rat in much the same way it has been done by other investigators using cocaine and opioids. 5. (-) MDMA, which is thought to act primarily by releasing serotonin, has a similar potency and efficacy as a reinforcer in the monkey as (+) MDMA, which is thought to act primarily by increasing levels of dopamine. Therefore, serotonin-releasing drugs may function as reinforcers, whereas serotonin agonists (e.g., LSD) do not. To test this notion, the ability of the isomers of other substituted phenyliospropylamines to maintain responding will be tested, and the effects of several serotonin antagonists and several dopamine antagonists on the reinforcing effects of these drugs will be measured as well. 6. We continue to evaluate the abuse liability of stimulants, hallucinogens, and sedatives as part of the research effort of the College on Problems of Drug Dependence. These drugs can be those that the WHO or the FDA is considering for scheduling decisions, drugs made by industrial or academic medicinal chemists, or industrial drugs that are being considered for clinical testing.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Wetherington, Cora Lee
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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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
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
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
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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