Methadone maintenance is currently the pharmacological treatment of choice dependence in the United States. Buprenorphine, a mixed agonist-antagonist opiate, has been proposed as an alternative to methadone in the treatment of opiate abuse. The current proposal is designed to compare these two treatments in terms of their efficacy in reducing opiate self-administration and in terms of the motivational deficits produced by the two drugs. Two of the studies proposed examine and compare the ability of methadone and buprenorphine to reduce self-administration of etonitazene (ETZ). Rats self-administering ETZ under an operant schedule and in their home cage will be treated with acute and chronic methadone and buprenorphine. In addition, the response cost for ETZ will be manipulated under the chronic regimen, to assess the contribution of this variable in suppressing opiate self-administration. A third study assesses the efficacy of making a highly preferred alternative reinforcer available during periods when the self- administered opiate is also available. A fourth study investigates the contribution the onset of abstinence symptoms plays as a mechanisms of action for ETZ self-administration. The motivational deficits produced by methadone treatment have been a continuing theme in our research throughout the previous project periods. The current research proposal continues this line of inquiry and extends it to allow comparison of motivational effects of methadone with those of buprenorphine. Four studies are dedicated to this theme. Two studies, one using rats and one using pigeons, compare buprenorphine and methadone effects under progressive ratio schedules. These schedules are used to assess reinforcer efficacy and strength and have shown consistent sensitivity to changes in motivational variables. Using the same schedule, another experiment assesses the effect that varying reinforcer quality will have on the dose-effect curves established under methadone and buprenorphine. The final experiment motivational properties of buprenorphine and methadone will compare these drugs under a schedule (multiple-5 ply VI) that purportedly is able to differentiate between motivational effects and motoric effects across drugs and doses.
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