Temporal parameters of enhanced opioid reward after initial opioid exposure in rats

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...

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Bibliographic Details
Published in:Psychopharmacology 2021-03, Vol.238 (3), p.725-734
Main Authors: Moerke, Megan J., Negus, S. Stevens
Format: Article
Language:English
Subjects:
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - pharmacology
Analysis
Animals
Biomedical and Life Sciences
Biomedicine
Brain - drug effects
Brain - metabolism
Brain stimulation rewards
Dosage
Dosage and administration
Drug abuse
Electric Stimulation
Electrical stimulation of the brain
ESB
Experiments
Intracranial self-stimulation
Male
Mere exposure effect
Morphine
Morphine - administration & dosage
Morphine - pharmacology
Narcotics
Neurosciences
Opioid receptors (type mu)
Opioids
Original Investigation
Pain - drug therapy
Pain - metabolism
Pain - psychology
Pharmacology/Toxicology
Psychiatry
Psychological aspects
Rats
Rats, Sprague-Dawley
Receptors, Opioid, mu - agonists
Reinforcement
Reward
Rodents
Self Stimulation - drug effects
Self-stimulation
Time Factors
Time-series analysis
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Summary: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.
ISSN:0033-3158
1432-2072
DOI:10.1007/s00213-020-05725-3