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  • Title: Self-injection of flunitrazepam alone and in the context of methadone maintenance in baboons.
    Author: Ator NA, Griffiths RR, Weerts EM.
    Journal: Drug Alcohol Depend; 2005 May 09; 78(2):113-23. PubMed ID: 15845314.
    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.
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