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

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.051425v1 306/3/1167    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 Sell, S. L. Articles by France, C. P. Search for Related Content PubMed PubMed Citation Articles by Sell, S. L. Articles by France, C. P.

BEHAVIORAL PHARMACOLOGY

Relative Efficacy of Buprenorphine, Nalbuphine and Morphine in Opioid-Treated Rhesus Monkeys Discriminating Naltrexone

Departments of Pharmacology (S.L.S., L.R.M., C.P.F.) and Psychiatry (C.P.F.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas

Efficacy is one determinant of whether a drug is an agonist or an antagonist under a particular set of conditions. Relative efficacy among the µ opioid receptor (MOR) ligands buprenorphine, nalbuphine, and morphine was examined in monkeys dependent on morphine (3.2 mg/kg/day) or L--acetylmethadol (LAAM) (1.0 mg/kg twice daily) and that discriminated naltrexone (0.0178 mg/kg) from saline. In morphine-treated monkeys, buprenorphine and not nalbuphine substituted for naltrexone. When administered before naltrexone in morphine-treated monkeys, morphine and nalbuphine shifted the naltrexone dose-effect curve to the right, while buprenorphine shifted the naltrexone dose-effect curve to the left. Under conditions of acute morphine deprivation, naltrexone-lever responding was slightly attenuated by buprenorphine and markedly attenuated by nalbuphine and morphine. In LAAM-treated monkeys, buprenorphine substituted completely for naltrexone in only one monkey, while nalbuphine and morphine failed to substitute in any monkey. When administered before naltrexone in LAAM-treated monkeys, buprenorphine, nalbuphine, and morphine dose dependently shifted the naltrexone dose-effect curve to the right, with the exception of one monkey in which buprenorphine shifted the naltrexone dose-effect curve to the left. These results demonstrate that a low efficacy MOR ligand can exert agonist or antagonist actions in the same animal depending on immediate pharmacologic history. The qualitatively different effects of buprenorphine in morphine- and LAAM-treated monkeys might be related to magnitude of dependence insofar as dependence can determine the efficacy required for agonist activity. Thus, buprenorphine has markedly different effects across different levels of opioid dependence.

Address correspondence to: Dr. Charles P. France, Department of Pharmacology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. E-mail: france{at}uthscsa.edu

This article has been cited by other articles:

				J.-X. Li, G. L. Becker, J. R. Traynor, Z.-H. Gong, and C. P. France Thienorphine: Receptor Binding and Behavioral Effects in Rhesus Monkeys J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 227 - 236. [Abstract] [Full Text] [PDF]

				D. A. White and S. G. Holtzman Discriminative Stimulus Effects of Acute Morphine Followed by Naltrexone in the Squirrel Monkey: A Further Characterization J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 374 - 382. [Abstract] [Full Text] [PDF]