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.