The studies proposed will evaluate the consequences of chronic exposure to benzodiazepines (BZs) on: (a) a fine-motor control task, and (b) the possible development of tolerance to their anxiolytic action. Also, (c) concurrent and historical pharmacological variables affecting the abuse potential of BZs, as assessed by the schedule-induced polydipsia techniques, will be explored. The behavioral and pharmacological properties of the residual """"""""rebound"""""""" state which can develop with chronic use of ultra-short-acting BZs will be analyzed with the motor task. Both caffeine and midazolam produce fine-motor task disruption when given alone; their acute and chronic interactive effects will evaluate whether caffeine-taking or its withdrawal ameliorates or exacerbates this disruption. The minimally-effective doses of various anxiolytic agents on a saline-ingestion test have correlated highly with their clinical efficacies. This test, and an extension of it, will be applied to the analysis of new putative anxiolytics, as well as to the problem of possible tolerance development to anxiolytic action. Serum drug levels will be tracked and related to the consequences of chronic drug-taking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA003117-07
Application #
3207719
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1982-01-15
Project End
1992-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Rutgers University
Department
Type
Schools of Arts and Sciences
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Lau, C E (1992) Determination of cocaethylene, cocaine and their metabolites in rat serum microsamples by high-performance liquid chromatography, and its application to pharmacokinetic studies in rodents. J Chromatogr 582:167-72
Williams, S L; Tang, M; Falk, J L (1992) Prior exposure to a running wheel and scheduled food attenuates polydipsia acquisition. Physiol Behav 52:481-3
Lau, C E; Dolan, S; Tang, M et al. (1991) Behavioral tolerance to flurazepam. Pharmacol Biochem Behav 38:823-7
Falk, J L; Lau, C E (1991) Synergism by caffeine and by cocaine of the motor control deficit produced by midazolam. Pharmacol Biochem Behav 39:525-9
Lau, C E; Falk, J L (1991) Sustained synergism by chronic caffeine of the motor control deficit produced by midazolam. Pharmacol Biochem Behav 40:723-31
Vigorito, M; Lau, C E; Tang, M et al. (1991) Midazolam withdrawal and discriminative motor control: effects of FG 7142 and Ro 15-1788. Pharmacol Biochem Behav 39:351-9
Tang, M; Falk, J L (1990) Schedule-induced oral self-administration of cocaine and ethanol solutions: lack of effect of chronic desipramine. Drug Alcohol Depend 25:21-5
Lau, C E; Falk, J L; Tang, M (1990) Motor performance decrement by midazolam: antagonism by Ro 15-1788 and CGS 8216. Pharmacol Biochem Behav 36:139-43
Culberson, J W; Tang, M; Lau, C E et al. (1990) Diazepam and discriminative motor control: acute, chronic and withdrawal effects. Pharmacol Biochem Behav 35:419-27
Falk, J L; vigorito, M; Tang, M et al. (1990) Schedule-induced cocaine drinking: choice between cocaine and vehicle. Pharmacol Biochem Behav 35:187-93

Showing the most recent 10 out of 24 publications