Research PapersHigh rates of midazolam self-administration in squirrel monkeysMunzar, P.a; Yasar, S.b; Redhi, G.H.a; Justinova, Z.a; Goldberg, S.R.aAuthor Information a Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA; b Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA *Present address: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298, USA. Correspondence to S.R. Goldberg, Preclinical Pharmacology Section, IRP, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. E-mail: [email protected] Received 4 October 2000 Revised 15 May 2001 Accepted 15 May 2001 Behavioral Pharmacology: July 2001 - Volume 12 - Issue 4 - p 257-265 Buy Abstract Although benzodiazepines are frequently abused by humans, they usually maintain lower rates of self-administration behavior in laboratory animals than other drugs of abuse such as psychomotor stimulants or barbiturates. In the present study, intravenous (i.v.) self-administration of the short-acting benzodiazepine midazolam was evaluated in squirrel monkeys. Monkeys (n = 3) initially self-administered the short-acting barbiturate methohexital (100#μg/kg/injection) during daily 1-hour sessions under a fixed-ratio 10, 60 s time-out, schedule of i.v. drug injection. This dose of methohexital maintained high rates of responding averaging 0.9 responses per second. Midazolam was then substituted for methohexital, and midazolam dose was subsequently varied from 0.3 to 3 μg/kg/injection. Each dose of midazolam was tested for five consecutive sessions and each unit dose condition was separated by five sessions of vehicle extinction. The midazolam dose–response function was an inverted U-shaped curve, with maximal rates of self-administration responding averaging 1.01 responses/second at a dose of 1 μg/kg/injection (an average of 48 injections per 1-hour session). The rates and fixed-ratio patterns of responding maintained by self-administration of midazolam in the present study were comparable to the rates and patterns of responding maintained in squirrel monkeys by self-administration of other drugs of abuse, including cocaine, amphetamine, nicotine and tetrahydrocannabinol, under similar experimental conditions. © 2001 Lippincott Williams & Wilkins, Inc.