title: Self-injection of flunitrazepam alone and in the context of methadone maintenance in baboons.
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.
authors.affiliation: Behavioral Biology Research Center, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, 5510 Nathan Shock Dr., Suite 3000, Baltimore, MD 21224, USA. ator@jhmi.edu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Ator
authors.forename: Roland R
authors.initials: RR
authors.lastname: Griffiths
authors.forename: Elise M
authors.initials: EM
authors.lastname: Weerts
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D005445:Flunitrazepam / Q000008:administration & dosage*; D018757:GABA Modulators / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008691:Methadone / Q000008:administration & dosage / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D010215:Papio; D012646:Self Administration
chemical_list: D018757:GABA Modulators; D005445:Flunitrazepam; D008691:Methadone