Action of Reserpine in Morphine Tolerant Rats: Absence of an Antagonism of Catecholamine Depletion
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
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The mechanism of resistance to the catecholamine depleting effects of reserpine in morphine tolerant rats was examined. In vitro, morphine did not alter reserpine inhibition of 3H-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 injection of 3H-reserpine. Animals chronically treated with morphine and with only partially reduced norepinephrine concentrations exhibited tritium levels less than one-half those of controls. It is concluded that an increased resistance to reserpine cannot be correlated with CNS tolerance to morphine.