title: Morphine intake and the effects of naltrexone and buprenorphine on the acquisition of methamphetamine intake.
abstract: Some common genetic factors appear to influence risk for drug dependence across multiple drugs of abuse. In previous research, mice that were selectively bred for higher amounts of methamphetamine consumption, using a two-bottle choice methamphetamine drinking procedure, were found to be less sensitive to the locomotor stimulant effects of morphine and of the more selective μ-opioid receptor agonist fentanyl, compared to mice that were bred for low methamphetamine consumption. This suggested that μ-opioid receptor-mediated pathways may influence genetic risk for methamphetamine consumption. We hypothesized that these differences in opioid sensitivity would impact opioid intake in the methamphetamine drinking lines and that drugs with μ-opioid receptor activity would impact methamphetamine intake. Consumption of morphine was examined in 2, two-bottle choice studies, one that compared morphine to quinine consumption and another that used a saccharin fading procedure. Next, naltrexone (0, 0.5, 1, 2, 5, 10 and 20 mg/kg), a μ-opioid receptor antagonist, and buprenorphine (0, 1, 2 or 4 mg/kg), a μ-opioid receptor partial agonist, were each examined for their effects on the acquisition of methamphetamine consumption. Low methamphetamine drinking mice consumed more morphine compared to high methamphetamine drinking mice. Naltrexone did not alter methamphetamine consumption in either selected line; however, buprenorphine reduced methamphetamine intake in the high methamphetamine drinking line. These data show that greater sensitivity to opioids is associated with greater opioid intake and warrant further investigation of drugs with μ-opioid receptor-specific agonist activity in genetically determined differences in methamphetamine consumption.
authors.affiliation: Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University.
authors.forename: E C
authors.initials: EC
authors.lastname: Eastwood
authors.forename: T J
authors.initials: TJ
authors.lastname: Phillips
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology* / Q000627:therapeutic use; D002755:Choice Behavior / Q000187:drug effects; D005260:Female; D007178:Inbreeding; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology*; D012641:Selection, Genetic
chemical_list: D009292:Narcotic Antagonists; D002047:Buprenorphine; D008694:Methamphetamine; D009271:Naltrexone; D009020:Morphine
keywords: addiction; amphetamine; opioid; psychostimulant; quinine; reward; saccharin; selective breeding; two-bottle choice drinking; μ-Opioid receptor