Self-injection of flunitrazepam alone and in the context of methadone maintenance in baboons

Drug Alcohol Depend. 2005 May 9;78(2):113-23. doi: 10.1016/j.drugalcdep.2004.09.007. Epub 2004 Dec 9.

Abstract

Patients in methadone maintenance programs use benzodiazepines to "boost" methadone's subjective effects, and flunitrazepam has been prominent in this context. Self-administration of flunitrazepam (0.001-0.32 mg/kg i.v.) alone and during daily oral methadone administration was evaluated in three baboons. Flunitrazepam maintained self-injection as an inverted U-shaped function of dose at rates higher than those maintained by most other benzodiazepines under the same procedure. In the context of demonstrated physical dependence on 3.2 mg/kg/day p.o. methadone, flunitrazepam doses on the ascending limb of the dose-effect curve maintained greater rates of self-injection than before methadone in two baboons. When the methadone dose decreased to 1.8 mg/kg/day, self-injection remained higher for those baboons and became higher than before methadone for the third baboon. Self-injection remained higher when methadone decreased to 1.0 mg/kg/day, except self-injection of the lowest flunitrazepam dose returned to or below the pre-methadone rate for two baboons. After methadone was discontinued, the dose-effect curve shifted to the right in one baboon but remained to the left in two. Flunitrazepam thus served as a reinforcer alone and in the context of methadone maintenance. Lower doses maintained higher self-injection during and shortly after methadone maintenance. Further research should explore the duration of higher self-injection rates following methadone maintenance.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Feeding Behavior / drug effects
  • Flunitrazepam / administration & dosage*
  • GABA Modulators / administration & dosage*
  • Injections, Intravenous
  • Methadone / administration & dosage
  • Methadone / therapeutic use*
  • Opioid-Related Disorders / drug therapy*
  • Papio
  • Self Administration

Substances

  • GABA Modulators
  • Flunitrazepam
  • Methadone