Journal
BEHAVIOURAL PHARMACOLOGY
Volume 23, Issue 7, Pages 678-692Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FBP.0b013e328358593c
Keywords
drug abuse; efficacy; intracranial self-stimulation; morphine; opioid; rat
Funding
- NIH [R01-NS070715, T32-DA007027]
- Jordan University of Science and Technology
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The net effect of g-opioid receptor agonists on intracranial self-stimulation (ICSS) in rats reflects an integration of rate-increasing and rate-decreasing effects. Previous opioid exposure is associated with tolerance to rate-decreasing effects and the augmented expression of abuse-related rate-increasing effects. This finding was replicated here with morphine. Subsequent studies then tested the hypothesis that opioid agonist-induced rate-decreasing effects require the activation of a larger relative fraction of mu receptors, and hence are more vulnerable to tolerance-associated reductions in receptor density than rate-increasing effects. Two sets of experiments were conducted to test this hypothesis. First, the effects of morphine on ICSS were examined after pretreatment with the irreversible g antagonist beta-funaltrexamine to reduce the density of available mu receptors. Second, effects were examined for a range of mu opioids that varied in relative efficacy at g receptors. The hypothesis predicted that (a) morphine, after beta-funaltrexamine treatment, or (b) low-efficacy mu agonists would mimic the effects of morphine tolerance to produce the reduced expression of rate-decreasing effects and enhanced expression of rate-increasing effects. Neither of these predictions were supported. These results indicate that mu agonist-induced facilitation and depression of ICSS may be mediated by distinct populations of mu receptors that respond differently to regimens of opioid exposure. Behavioural Pharmacology 23:678-692 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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