EFFECTS OF SELECTIVE OPIOID RECEPTOR ANTAGONISTS ON MORPHINE-INDUCED CHANGES IN STRIATAL AND LIMBIC DOPAMINE METABOLISM

The effects of selective opioid receptor antagonists, beta-funaltrexam ine (selective for mu receptor), naloxonazine (mu l) and naltrindole ( delta) on morphine-induced changes in striatal and limbic dopamine (DA ) metabolism were studied in rats. beta-Funaltrexamine (20 mu g intrac erebroventricularly) and naloxonazine (15 mg/kg intraperitoneally) wer e given 24 hr before morphine (15 mg/kg subcutaneously), and the rats were decapitated 60 min. after morphine. Naltrindole (1 mg/kg intraper itoneally) was given twice, 15 min. before and after morphine. Morphin e significantly increased the concentrations of DA metabolites 3,4-dih ydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This effe ct was significantly antagonized by pretreatment with beta-funaltrexam ine but not by naloxonazine or naltrindole. However, naloxonazine atte nuated the antinociceptive effect of morphine in the hot-plate test. T he concentration of DA was not significantly altered by any of the dru gs studied. These results show that selective blockade of mu-opioid re ceptors totally blocks the increase of striatal and limbic DA metaboli sm induced by morphine. It seems that mu 2-subtype of mu-opioid recept or predominantly mediates this effect. Blockade of delta-opioid recept or did not alter these effects of morphine.