The net effect of μ-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 μ 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 μ antagonist β-funaltrexamine to reduce the density of available μ receptors. Second, effects were examined for a range of μ opioids that varied in relative efficacy at μ receptors. The hypothesis predicted that (a) morphine, after β-funaltrexamine treatment, or (b) low-efficacy μ 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 μ agonist-induced facilitation and depression of ICSS may be mediated by distinct populations of μ receptors that respond differently to regimens of opioid exposure.
- drug abuse
- intracranial self-stimulation
ASJC Scopus subject areas
- Psychiatry and Mental health