Benzodiazepine drugs are among the most widely prescribed of all medications, and there is increasing concern about misuse and abuse of these compounds. This project will investigate the reinforcing, discriminative stimulus, and physiological-dependence producing properties of benzodiazepine-like drugs in baboons and rats. Three interrelated sets of experiments will be conducted. One set of experiments will use drug self-administration procedures. Two experiments will investigate various environmental and pharmacological factors which may enhance and/or modulate intravenous benzodiazepine self-administration, while another study will compare the oral self-administration of a series of benzodiazepines. A second set of experiments will use drug discrimination procedures. These studies will explore molecular mechanisms of action of benzodiazepine-like drugs and characterize interactions between benzodiazepines and opioids. The third set of experiments will use antagonist precipitated withdrawal procedures to help characterize physiological dependence on and mechanisms of action of benzodiazepine-like drugs. Overall, the experiments will provide information relevant to the abuse/dependence liability and behavioral, pharmacological, and molecular mechanisms of action of benzodiazepine-like drugs. More generally, scientific characterization of the benzodiazepine-like compounds will provide information concerning the major health problems of drug abuse. Data from this project will ultimately have clincal relevance in the treatment and prevention of drug abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA001147-11
Application #
3206862
Study Section
(SRC)
Project Start
1975-02-01
Project End
1988-02-29
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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
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, 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
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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