QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.095380v1 317/2/711    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Negus, S. S. Search for Related Content PubMed PubMed Citation Articles by Negus, S. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HEROIN METHADONE NALOXONE

BEHAVIORAL PHARMACOLOGY

Choice between Heroin and Food in Nondependent and Heroin-Dependent Rhesus Monkeys: Effects of Naloxone, Buprenorphine, and Methadone

Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, Belmont, Massachusetts

Several medications are approved for treatment of opiate abuse, but determinants of their clinical effectiveness are not completely understood. States of opiate dependence or withdrawal may constitute one important set of determinants. To test this hypothesis, the effects of naloxone, buprenorphine, and methadone were assessed on choice between heroin and food in nondependent rhesus monkeys and in heroin-dependent monkeys undergoing withdrawal. A choice procedure was used to permit dissociation of medication effects on the relative reinforcing properties of heroin from nonselective effects on response rates. In nondependent monkeys, increasing unit doses of heroin (0-0.1 mg/kg/injection) maintained dose-dependent increases in heroin choice. Chronic 5-day treatment with naloxone (0.01-0.32 mg/kg/h) or buprenorphine (0.01-0.1 mg/kg/day) produced dose-dependent rightward shifts in heroin choice dose-effect curves, whereas chronic methadone (0.1-0.56 mg/kg/h) had little effect on heroin choice up to doses that suppressed responding. In heroin-dependent monkeys, opiate withdrawal produced overt abstinence signs as well as increases in heroin choice, manifested as leftward shifts in heroin choice dose-effect curves. The withdrawal-associated increases in heroin choice suggest that opiate withdrawal increased the relative reinforcing efficacy of heroin in comparison with food, an effect that may be related to relapse in humans. Methadone prevented withdrawal-associated increases in heroin choice, whereas buprenorphine was less effective. These findings suggest that agonist medications such as methadone may derive their clinical utility from their ability to attenuate withdrawal-associated increases in opiate reinforcement. Moreover, this procedure may be useful for exploring mechanisms underlying withdrawal-associated increases in opiate reinforcement and for testing candidate medications.

Address correspondence to: Stevens Negus, Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02178-9106. E-mail: negus{at}mclean.harvard.edu

This article has been cited by other articles:

				Z. D. Cooper, Y. N.-T. Truong, Y.-G. Shi, and J. H. Woods Morphine Deprivation Increases Self-Administration of the Fast- and Short-Acting {micro}-Opioid Receptor Agonist Remifentanil in the Rat J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 920 - 929. [Abstract] [Full Text] [PDF]

				J. Bergman and C. A. Paronis Measuring the reinforcing strength of abused drugs. Mol. Interv., October 1, 2006; 6(5): 273 - 283. [Abstract] [Full Text] [PDF]