Acute opioid pretreatment potentiates naltrexone-induced drinking suppression in water-deprived rats

Pretreatment with morphine-like agonists potentiates the behavioral effects of opioid antagonists, possibly reflecting a state of acute physical depen dence. Several studies have used operant behavior to quantify these effects . However, little research has been done using unconditioned behavior. One objective of this study was to determine whether opioid agonist pretreatmen t (e.g., morphine, fentanyl, and meperidine) potentiated naltrexone-induced suppression of water consumption following deprivation. Another objective was to determine whether the agonist pretreatment interval was functionally related to efficacy for the manifestation of acute dependence. Finally, we compared temporally the effects of the three agonists. Adult male Sprague- Dawley rats were water deprived for 18, 20, or 22 h and given an injection (s.c.) of an agonist or saline. After 1.75, 3.75, or 5.75 h, animals receiv ed a single dose (s.c.) of naltrexone (0.01-30 mg/kg) or saline. Fifteen mi nutes later, subjects had access to water for 30 min. A time course of anti nociception was constructed after agonist administration, using the tail-fl ick procedure. All three agonists dose dependently potentiated naltrexone-i nduced drinking suppression, decreasing the ED50 of naltrexone by as much a s 150-fold. There was no clear relationship between agonist efficacy and pr etreatment interval. Sensitization to naltrexone was seen up to 6 h after a gonist administration, occurring in the apparent absence of an antinocicept ive effect. These data extend the range of behavioral effects of opioid ant agonists potentiated by opioid agonist pretreatment to suppression of drink ing and show that such potentiation can occur in the absence of a prototypi cal agonist effect.