Effects of selective opioid receptor antagonists on morphine-induced changes in striatal and limbic dopamine metabolism.
The effects of selective opioid receptor antagonists, beta-funaltrexamine (selective for mu receptor), naloxonazine (microliter) and naltrindole (delta) on morphine-induced changes in striatal and limbic dopamine (DA) metabolism were studied in rats. beta-Funaltrexamine (20 micrograms intracerebroventricularly) and naloxonazine (15 mg/kg intraperitoneally) were given 24 hr before morphine (15 mg/kg subcutaneously), and the rats were decapitated 60 min. after morphine. Naltrindole (1 mg/kg intraperitoneally) was given twice, 15 min. before and after morphine. Morphine significantly increased the concentrations of DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This effect was significantly antagonized by pretreatment with beta-funaltrexamine but not by naloxonazine or naltrindole. However, naloxonazine attenuated the antinociceptive effect of morphine in the hot-plate test. The concentration of DA was not significantly altered by any of the drugs studied. These results show that selective blockade of mu-opioid receptors totally blocks the increase of striatal and limbic DA metabolism induced by morphine. It seems that mu 2-subtype of mu-opioid receptor predominantly mediates this effect. Blockade of delta-opioid receptor did not alter these effects of morphine.
Piepponen
T P
TP
Department of Pharmacy, University of Helsinki, Finland.
Ahtee
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity*; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000633:toxicity*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
D009292:Narcotic Antagonists; D009294:Narcotics; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D015102:3,4-Dihydroxyphenylacetic Acid; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; C034643:naloxonazine; C055382:naltrindole; D004298:Dopamine; D006719:Homovanillic Acid