Action of reserpine in morphine-tolerant rats: absence of an antagonism of catecholamine depletion.

The mechanism of resistance to the catecholamine depleting effects of reserpine in morphine tolerant rats was examined. In vitro, morphine did not alter reserpine 3 inhibition of H-norepinephrine uptake by synaptic vesicles. Similarly, uptake by vesicles isolated from morphine tolerant animals was as susceptible to reserpine inhibition as that of corresponding preparations from saline treated controls. Consistent with earlier reports, intraperitoneally administered reserpine only partially reduced brain catecholamine levels in most rats treated chronically with morphine. However, reserpine injected intravenously depleted norepinephrine and dopamine in experimental animals to the same extent as controls treated by either route of administration. The amount of reserpine which actually reached the brain was estimated by intraperitoneal 3 injection of H-reserpine. Animals chronically treated with morphine and with only partially reduced norepinephrine concentrations exhibited tritium levels less than onehalf those of controls. It is concluded that an increased resistance to reserpine cannot be correlated with CNS tolerance to morphine. Rather, degradation or excretion of reserpine may be enhanced peripherally as a result of chronic morphine treatment.