EFFECT OF MORPHINE ON STRIATAL DOPAMINE METABOLISM AND ASCORBIC-ACID AND URIC-ACID RELEASE IN FREELY MOVING RATS

Recent ex vivo findings have shown that morphine increases dopamine (D A) and xanthine oxidative metabolism and ascorbic acid (AA) oxidation in the rat striatum. In the present study, we evaluated the effects of subcutaneous daily morphine (20 mg/kg) administration on DA, dihydrox yphenylacetic acid (DOPAC), homovanillic acid (HVA), AA and uric acid in the striatum of freely moving rats using microdialysis. Dialysates were assayed by high performance liquid chromatography with electroche mical detection. On the first day, morphine administration caused a si gnificant increase in extracellular DA, DOPAC, HVA, AA and uric acid c oncentrations over a 3 h period after morphine. In all treated rats (n =7), individual concentrations of DOPAC+HVA were directly correlated w ith individual AA and uric acid concentrations. Last morphine administ ration on the 4th day increased DOPAC, HVA, AA and uric acid Concentra tions but failed to increase those of DA. Individual DOPAC+HVA concent rations were still directly correlated with individual AA and uric aci d concentrations. These results suggest that systemic morphine increas es both striatal DA release and DA and xanthine oxidative metabolism O nly the former effect undergoes tolerance. The increase in DA oxidativ e metabolism is highly correlated with that of xanthine. The subsequen t enhancement in reactive oxygen species production may account for th e increase in extracellular AA.