Megan J Moerke1,2, S Stevens Negus3. 1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 N. 12th St., Richmond, VA, 23298, USA. 2. Division of Preclinical Pharmacology, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd., Baltimore, MD, 21224, USA. 3. Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 N. 12th St., Richmond, VA, 23298, USA. sidney.negus@vcuhealth.org.
Abstract
RATIONALE: Mu opioid receptor agonists are indispensable for the treatment of pain, but clinical use carries the inherent risk of transition from effective treatment to abuse. Abuse potential appears to increase rapidly during periods of initial opioid exposure in humans, and this increase in opioid reward during initial opioid exposure can be modeled in rats using an intracranial self-stimulation (ICSS) procedure. OBJECTIVES: The goal of the present study was to examine temporal parameters of this phenomenon. METHODS: Adult male Sprague-Dawley rats responded for electrical brain stimulation using a frequency-rate ICSS procedure. In the first experiment, rats received daily morphine injections for 6 days, and morphine effects on ICSS were re-determined 1 day, 1 week, or 1 month after the repeated morphine treatment regimen to evaluate the persistence of enhanced opioid reward. In the second experiment, rats received six repeated morphine injections with different interdose intervals (two per day, one per day, every other day, every fourth day), and morphine effects were re-determined 1 day after the last dose to determine dosing frequencies sufficient to produce enhanced opioid reward. RESULTS: Results of the first experiment indicated that enhanced opioid reward was greatest 1 day after the morphine treatment regimen and completely dissipated after 4 weeks. The second experiment indicated that all dosing frequencies tested were sufficient to produce enhanced reward. CONCLUSIONS: Taken together, these results suggest that enhancement of opioid reward after initial opioid exposure is relatively transient but can be produced by a range of different dosing frequencies.
RATIONALE: Mu opioid receptor agonists are indispensable for the treatment of pain, but clinical use carries the inherent risk of transition from effective treatment to abuse. Abuse potential appears to increase rapidly during periods of initial opioid exposure in humans, and this increase in opioid reward during initial opioid exposure can be modeled in rats using an intracranial self-stimulation (ICSS) procedure. OBJECTIVES: The goal of the present study was to examine temporal parameters of this phenomenon. METHODS: Adult male Sprague-Dawley rats responded for electrical brain stimulation using a frequency-rate ICSS procedure. In the first experiment, rats received daily morphine injections for 6 days, and morphine effects on ICSS were re-determined 1 day, 1 week, or 1 month after the repeated morphine treatment regimen to evaluate the persistence of enhanced opioid reward. In the second experiment, rats received six repeated morphine injections with different interdose intervals (two per day, one per day, every other day, every fourth day), and morphine effects were re-determined 1 day after the last dose to determine dosing frequencies sufficient to produce enhanced opioid reward. RESULTS: Results of the first experiment indicated that enhanced opioid reward was greatest 1 day after the morphine treatment regimen and completely dissipated after 4 weeks. The second experiment indicated that all dosing frequencies tested were sufficient to produce enhanced reward. CONCLUSIONS: Taken together, these results suggest that enhancement of opioid reward after initial opioid exposure is relatively transient but can be produced by a range of different dosing frequencies.
Entities:
Keywords:
Abuse; Intracranial self-stimulation; Morphine; Mu opioid receptor agonist; Tolerance
Authors: T R Baird; H I Akbarali; W L Dewey; H Elder; M Kang; S A Marsh; M R Peace; J L Poklis; E J Santos; S S Negus Journal: Psychopharmacology (Berl) Date: 2022-02-24 Impact factor: 4.530