title: Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus.
abstract: Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects.
authors.affiliation: Department of Psychological Science, Georgia Regents University.
authors.forename: Laurence L
authors.initials: LL
authors.lastname: Miller
authors.affiliation: Department of Pharmacology, Jordan University of Science and Technology.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Altarifi
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University.
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine