Restraint stress potentiates analgesia induced by 5'-N-ethylcarboxamidoadenosine: comparison with morphine.
mu-Opioid receptor agonists, e.g. morphine, produce analgesia that can be potentiated by restraint stress. Adenosine receptor agonists, e.g. 5'-N-ethylcarboxamidoadenosine (NECA), also produce analgesia. To determine if adenosine-induced analgesia is also potentiated by stress, dose- and time-effect curves for NECA (0.01-0.1 mg/kg s.c.) were generated in adult male Sprague-Dawley rats either unrestrained or restrained in Plexiglas cylinders, using the tail-flick assay. Morphine (1.0-5.6 mg/kg s.c.) was also tested for comparison. Both compounds produced dose-dependent increases in tail-flick latencies. This effect of both drugs was potentiated in restrained rats. The opioid receptor antagonist, naltrexone (1.0 mg/kg s.c.) blocked completely the effect of morphine in both groups and attenuated the stress-induced potentiation of NECA-induced analgesia. The adenosine receptor antagonist, caffeine (10.0 mg/kg s.c.), blocked the analgesic effect of NECA but not that of morphine. These results indicate that adenosine-mediated analgesia is potentiated by restraint stress and suggest a role for endogenous opioids in the mediation of stress-induced potentiation of analgesia.
Woolfolk
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DR
Emory University School of Medicine, Atlanta, GA 30322.
Holtzman
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SG
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000698:Analgesia; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology*
D011957:Receptors, Opioid; D019830:Adenosine-5'-(N-ethylcarboxamide); D002110:Caffeine; D009271:Naltrexone; D009020:Morphine; D000241:Adenosine