Research in baboons is proposed to characterize the intravenous reinforcing and physical dependence-producing effects of benzodiazepines and also to examine caffeine reinforcement interactions with cocaine and nicotine. Two self-injection studies will determine whether physical dependence enhances the reinforcing effects of a benzodiazepine. A series of three studies will address concerns that the abuse liability of benzodiazepines is enhanced by interactions with opioids by determining whether chronic opioid exposure increases benzodiazepine self-injection and whether the discriminative stimulus effects of benzodiazepines and opioids mutually potentiate each other. One study will determine whether the abuse liability of sedative drugs can be reduced by slowing the rate of drug onset. A final self-injection study will explore the concern that flunitrazepam has a particularly high abuse liability. A second series of studies will examine benzodiazepine physical dependence. Studies will examine precipitated withdrawal effects produced by a series of novel partial/selective benzodiazepine receptor agonists in benzodiazepine-dependent baboons. Another study will use drug discrimination methods to examine the effects of these same compounds in benzodiazepine-dependent baboons that have been trained to discriminate the benzodiazepine antagonist flumazenil. A third study will explore using an antagonist to decrease the severity and/or shorten the time course of the spontaneous withdrawal syndrome. Finally, two studies will explore recent findings suggesting that caffeine potentiates the reinforcing effects of cocaine and nicotine by characterizing the effects of caffeine on the self-injection of cocaine and nicotine, and the effects of cocaine and nicotine on caffeine self-injection. Benzodiazepines are among the most widely prescribed of all psychotropic medications and caffeine is the most widely used psychotropic drug in the world. There are health risk concerns about benzodiazepine abuse and physical dependence among polydrug abusers and patients, and also about excessive caffeine use in a significant portion of the population. This research will advance our understanding of factors which contribute to the overuse, abuse and dependence on these widely self-administered drugs, provide valuable insights into possible interactions of these drugs with other widely abused drugs, and will ultimately contribute to the development of improved prevention, control and treatment procedures for various forms of drug abuse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Human Development Research Subcommittee (NIDA)
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Schnur, Paul
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Johns Hopkins University
Schools of Medicine
United States
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Ator, Nancy A; Griffiths, Roland R; Weerts, Elise M (2005) Self-injection of flunitrazepam alone and in the context of methadone maintenance in baboons. Drug Alcohol Depend 78:113-23
Weerts, Elise M; Ator, Nancy A; Kaminski, Barbara J et al. (2005) Comparison of the behavioral effects of bretazenil and flumazenil in triazolam-dependent and non-dependent baboons. Eur J Pharmacol 519:103-13
Weerts, Elise M; Griffiths, Roland R (2003) The adenosine receptor antagonist CGS15943 reinstates cocaine-seeking behavior and maintains self-administration in baboons. Psychopharmacology (Berl) 168:155-63
Ator, Nancy A; Griffiths, Roland R (2003) Principles of drug abuse liability assessment in laboratory animals. Drug Alcohol Depend 70:S55-72
Kaminski, B J; Sannerud, C A; Weerts, E M et al. (2003) Physical dependence in baboons chronically treated with low and high doses of diazepam. Behav Pharmacol 14:331-42
Weerts, E M; Griffiths, R R (1999) Evaluation of the intravenous reinforcing effects of clonidine in baboons. Drug Alcohol Depend 53:207-14
Weerts, E M; Ator, N A; Griffiths, R R (1999) Comparison of the intravenous reinforcing effects of propofol and methohexital in baboons. Drug Alcohol Depend 57:51-60
Weerts, E M; Griffiths, R R (1999) Evaluation of limited and unlimited food intake during withdrawal in triazolam-dependent baboons. Behav Pharmacol 10:415-21
Weerts, E M; Ator, N A; Grech, D M et al. (1998) Zolpidem physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons. J Pharmacol Exp Ther 285:41-53
Weerts, E M; Griffiths, R R (1998) Zolpidem self-injection with concurrent physical dependence under conditions of long-term continuous availability in baboons. Behav Pharmacol 9:285-97

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