Large, daily voluntary intakes of benzodiazepine (BZ) solutions will be produced in rats by the technique of schedule-induced overindulgence. The elevated drug solution ingestion levels for flurazepam and chlordiazepoxide will be compared with vehicle (water) ingestion over a range of inducing conditions both in fluid acceptance and preference situations. Results will be related to blood drug and metabolite levels and to similar ingestion arrangements with etonitazene. Physical dependence on BZ's will be evaluated: (1) both by withdrawal and by precipitation with BZ antagonists with audiogenic triggering, and (2) by changes in a discriminative fine motor control performance in separate experiments. The motor studies involve a force-transducer-holding steadiness test and will also explore the acute, chronic, withdrawal and precipitated withdrawal from flurazepam and diazepam. A number of anxiolytic and putative anxiolytic agents will be evaluated by an NaCl solution ingestion procedure. Median effective doses will be determined for phenobarbital, diazepam, oxazepam, trifluoperizine, reserpine, PCP, zopiclone, Ro 5-4864, clobazam and tracazolate in order to develop a testing procedure for anxiolytic activity in addition to the standard conflict tests.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003117-05
Application #
3207720
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1982-01-15
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
5
Fiscal Year
1986
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

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