title: Lack of evidence for opioid tolerance or dependence in rhesus monkeys following high-dose anabolic-androgenic steroid administration.
abstract: Prolonged use of high-dose anabolic-androgenic steroids (AAS) may induce a dependence syndrome, and emerging evidence suggests that AAS effects on endogenous opioid systems may contribute to AAS abuse. The present study tested the hypothesis that high dose AAS treatment enhances endogenous opioid activity in rhesus monkeys as revealed by 1) tolerance to the antinociceptive effects of the mu opioid agonist morphine and 2) physical dependence as indicated by evidence of opioid withdrawal following administration of the opioid antagonist naloxone. Three rhesus monkeys were treated for 14 days with 3.2 mg/kg/day testosterone propionate, and the effects of morphine (0.32-10 mg/kg) and naloxone (0.01-0.32 mg/kg) were examined both before and during treatment. Morphine antinociception was evaluated using a warm-water tail-withdrawal procedure, and naloxone-precipitated withdrawal was evaluated using checked behavioral signs and measures of ventilatory rate. Chronic testosterone administration for 14 days produced a 100-fold increase in mean plasma testosterone levels. However, testosterone treatment did not significantly alter the antinociceptive effects of morphine, and naloxone did not precipitate signs of opioid withdrawal either before or during testosterone treatment. These data do not support the hypothesis that high-dose AAS treatment enhances endogenous opioid activity in rhesus monkeys in a way that produces opioid tolerance or dependence.
authors.affiliation: Alcohol and Drug Abuse Research Center: Behavioral Science Laboratory, McLean Hospital-Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA. negus@mclean.harvard.edu
authors.forename: S S
authors.initials: SS
authors.lastname: Negus
authors.forename: H G
authors.initials: HG
authors.lastname: Pope
authors.forename: G
authors.initials: G
authors.lastname: Kanayama
authors.forename: J D
authors.initials: JD
authors.lastname: Wines
authors.forename: B D
authors.initials: BD
authors.lastname: Fischer
mesh_terms: D045930:Anabolic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006358:Hot Temperature; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone; D009292:Narcotic Antagonists; D009294:Narcotics / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D013739:Testosterone / Q000097:blood
chemical_list: D045930:Anabolic Agents; D000701:Analgesics, Opioid; D000728:Androgens; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D013739:Testosterone; D009020:Morphine