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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA002717-08
Application #
3207525
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1980-09-01
Project End
1991-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Arts and Sciences
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Jewett, D C; Cleary, J; Levine, A S et al. (1995) Effects of neuropeptide Y, insulin, 2-deoxyglucose, and food deprivation on food-motivated behavior. Psychopharmacology (Berl) 120:267-71
Schuh, K J; Schaal, D W; Thompson, T et al. (1994) Insulin, 2-deoxy-D-glucose, and food deprivation as discriminative stimuli in rats. Pharmacol Biochem Behav 47:317-24
Kovera, C A; Schaal, D W; Thompson, T et al. (1994) Behavioral and neurochemical mechanisms of opioid-antidepressant interactions. Pharmacol Biochem Behav 48:47-52
Jewett, D C; Cleary, J; Schaal, D W et al. (1993) [Leu31,Pro34]neuropeptide Y (NPY), but not NPY 20-36, produces discriminative stimulus effects similar to NPY and induces food intake. Brain Res 631:129-32
Rudski, J M; Schaal, D W; Thompson, T et al. (1992) Effects of methadone on free feeding in satiated rats. Pharmacol Biochem Behav 43:1033-7
Jewett, D C; Cleary, J; Levine, A S et al. (1992) Effects of neuropeptide Y on food-reinforced behavior in satiated rats. Pharmacol Biochem Behav 42:207-12
Jewett, D C; Schaal, D W; Cleary, J et al. (1991) The discriminative stimulus effects of neuropeptide Y. Brain Res 561:165-8
Macenski, M J; Cleary, J; Thompson, T (1990) Effects on opioid-induced rate reductions by doxepin and bupropion. Pharmacol Biochem Behav 37:247-52
Poling, A; Cleary, J; Berens, K et al. (1990) Neuroleptics and learning: effects of haloperidol, molindone, mesoridazine and thioridazine on the behavior of pigeons under a repeated acquisition procedure. J Pharmacol Exp Ther 255:1240-5
Nader, M A; Thompson, T (1989) Interaction of reinforcement history with methadone on responding maintained under a fixed-interval schedule. Pharmacol Biochem Behav 32:643-9

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