Back to Search
Start Over
A leptin-mediated central mechanism in analgesia-enhanced opioid reward in rats.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2014 Jul 16; Vol. 34 (29), pp. 9779-88. - Publication Year :
- 2014
-
Abstract
- Opioid analgesics are commonly used in chronic pain management despite a potential risk of rewarding. However, it remains unclear whether opioid analgesia would enhance the opioid rewarding effect thereby contributing to opioid rewarding. Utilizing a rat paradigm of conditioned place preference (CPP) combined with ankle monoarthritis as a condition of persistent nociception, we showed that analgesia induced by either morphine or the nonsteroid anti-inflammatory drug ibuprofen increased CPP scores in arthritic rats, suggesting that analgesia itself had a rewarding effect. However, arthritic rats exhibited a significantly higher CPP score in response to morphine than ibuprofen. Thus, the rewarding effect of morphine was enhanced in the presence of persistent nociception, producing a phenomenon of analgesia-enhanced opioid reward. At the cellular level, administration of morphine activated a cascade of leptin expression, glial activation, and dopamine receptor upregulation in the nucleus accumbens (NAc), while administration of ibuprofen decreased glial activation with no effect on leptin expression in the NAc. Furthermore, the morphine rewarding effect was blocked in leptin deficient ob/ob mice or by neutralizing leptin or interleukin-1β in the NAc without diminishing morphine analgesia. The data indicate that systemic opioid can activate a leptin-mediated central mechanism in the NAc that led to the enhanced opioid rewarding effect. These findings provide evidence for an interaction between opioid analgesia and opioid rewarding, which may have implications in clinical opioid dose escalation in chronic pain management.<br /> (Copyright © 2014 the authors 0270-6474/14/349779-10$15.00/0.)
- Subjects :
- Animals
Animals, Newborn
Arthritis, Experimental complications
Astrocytes drug effects
Cerebral Cortex cytology
Conditioning, Operant drug effects
Conditioning, Operant physiology
Disease Models, Animal
Gene Expression Regulation drug effects
Gene Expression Regulation genetics
Leptin genetics
Leptin pharmacology
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mutation genetics
Pain etiology
Pain Measurement drug effects
Pain Threshold drug effects
Rats
Rats, Sprague-Dawley
Analgesics, Opioid administration & dosage
Leptin physiology
Morphine administration & dosage
Pain drug therapy
Reward
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 34
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 25031415
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.0386-14.2014