Psychopharmacology

, Volume 135, Issue 1, pp 70–81

Stable low-rate midazolam self-injection with concurrent physical dependence under conditions of long-term continuous availability in baboons

  • E. M. Weerts
  • Barbara J. Kaminski
  • Roland R. Griffiths
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130050487

Cite this article as:
Weerts, E., Kaminski, B. & Griffiths, R. Psychopharmacology (1998) 135: 70. doi:10.1007/s002130050487

Abstract

 The current research was undertaken to characterize intravenous midazolam self-injection and the concurrent development of physical dependence under conditions of continuous drug availability. Baboons (n=6) IV self-injected midazolam under conditions of continuous availability under a fixed-ratio 30 schedule of lever-pull responses with a 5-min time-out after each injection. Midazolam (1.0 mg/kg) maintained an orderly spaced within-day pattern of injections and low, but stable, daily rates of self-injection over 30 or more days (e.g. <20 injections/day). Sequential substitution of saline and then midazolam produced rapid extinction and then reinstatement of responding at the same stable rate. In subsequent manipulations, a range of lower doses of midazolam (0.0156–0.25 mg/kg) were also shown to reinstate self-injection responding after extinction on saline; however, both chronic and acute dose manipulations indicated that dose-regulation was poor. Chronic self-injection of the high dose (1.0 mg/kg) but not lower doses produced a suppression in responding maintained by food pellet delivery. Chronic self-injection of 1.0 and 0.25 mg/kg midazolam produced physical dependence as reflected in classic benzodiazepine spontaneous and flumazenil-precipitated withdrawal syndromes, including tremor, vomiting and, in one instance, seizure. The stable, low-rate self-injection of midazolam, with concurrent development of physical dependence, demonstrated in the present study may provide a useful model system for investigating factors which contribute to long-term inappropriate use of benzodiazepines by physically dependent patients.

Key words Benzodiazepines Anxiolytics Midazolam Flumazenil Self-administration Reinforcement Drug abuse Withdrawal Physical dependence Feeding Baboons 

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • E. M. Weerts
    • 1
  • Barbara J. Kaminski
    • 1
  • Roland R. Griffiths
    • 1
  1. 1.Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive/Suite 3000, Baltimore, MD 21224, USATP
  2. 2.Department of Neuroscience, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive/Suite 3000, Baltimore, MD 21224, USATP

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