EFFECTS OF MORPHINE ON THE RAT STRIATAL DOPAMINE METABOLISM

Concomitant with total suppression of the spontaneous unitary discharges of neurons in the rat corpus striatum, intracarotidly injected morphine (5 mg/kg) was also found to increase the levels of dopamine, homovanillic acid and cyclic AMP by 80, 65 and 46 per cent respectively, measured 5 min after injection. This provides further support to the hypothesis that the nigrostriatal dopaminergic pathway is stimulated by acutely administered morphine. Morphine (10-5-10-3 M) did not alter the activity of striatal tyrosine aminotransferase. The drug, added in vitro (10-6-10-4 M) or by intracarotid injection (5 mg/kg) did not affect the activity of striatal tyrosine hydroxylase. Moreover, morphine (10-4 M) did not interfere with the inhibitory effects of dopamine (10-6-10-4 M) on striatal tyrosine hydroxylase. However, it significantly potentiated the stimulatory effects of cyclic AMP on this enzyme. Morphine (10-5-10-4) was also found to have no effect on the spontaneous or K+-stimulated release of dopamine from striatal homogenate and synaptosomes. However, in the presence of 5 × 10-5 M and 10-4 M morphine, the uptake of dopamine by striatal homogenate was inhibited by 14 and 33 per cent respectively. With synaptosomal preparations, dopamine uptake was inhibited by 17 per cent in the presence of 10-4 M morphine-the inhibition being competitive with dopamine with an apparent Ki of 0.41 mM. The inhibition of dopamine uptake caused by 10-4 M morphine in either preparation was not reversed by the addition of 10-4 M naloxone. It was concluded that the increase in dopaminergic activity following acute treatment of morphine is probably due to (1) prolongation of the effect of dopamine on the post-synaptic neurons resulting in increased production of cyclic AMP which in turn potentiates dopamine synthesis and (2) decrease in presynaptic cystosol dopamine which is normally a feedback inhibitor of tyrosine hydroxylase thus leading to increased synthesis of dopamine. © 1979.