Stress-induced potentiation of morphine-induced analgesia in morphine-tolerant rats.
This study was designed to evaluate whether or not rats that were tolerant to the analgesic action of morphine were also tolerant to stress-induced potentiation of morphine-induced analgesia. Rats were trained to drink either solutions of morphine (0.5 mg/ml) or drug-free tap water on a limited access schedule (10 min every 6 hr). The daily intake of morphine averaged 46 mg/kg. Nontolerant and rats tolerant to morphine were tested for morphine-induced analgesia (tail-flick assay), while either unstressed or stressed (i.e. immobilized in Plexiglas cylinders). Morphine produced dose- and time-dependent increases in tail-flick latencies in all groups. Increased sensitivity to analgesia induced by morphine was evident for both nontolerant and tolerant, stressed rats, when compared to their unstressed counterparts. Stress-induced potentiation of morphine-induced analgesia was characterized by dose-related increases in the peak effect and duration of the effect. Stress potentiated the analgesic effect of morphine, comparably in nontolerant (1.7-fold) and tolerant (1.5-fold) rats. Differential tolerance to analgesia induced by morphine and to stress-induced potentiation of morphine-induced analgesia suggests that different mechanisms mediate these two effects.
Fleetwood
S W
SW
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Holtzman
S G
SG
D000701:Analgesics, Opioid; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000523:psychology*; D013997:Time Factors
D000701:Analgesics, Opioid; D009020:Morphine