Morphine-Induced Changes in Intracellular Catecholamines in Rat Central Nervous System,
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
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The effects of acute and chronic doses of morphine on intracellular levels and distribution of catecholamines CA were studied in the rat. Brain homogenates were fractioned into crude synaptosomal pellets and supernatants. The synaptosomes were osmotically shocked, and dopamine DA and norephinephrine NE levels were measured as bound synaptic vesicles, free extravesicular, and extrasynaptosomal fractions in the supernatant. The rate of synthesis of CA was determined by estimating conversion of injected CC14 tyrosine into CC14 DA and CC14 NE. Acute injections of morphine 60 mgkg body weight resulted in significant increases in the extrasynaptosomal and free fractions of NE. An increase in endogenous levels of DA was seen in the extrasynaptosomal CC14 DA at 30 and 60 min respectively. The bound fractions demonstrated no appreciable differences at any of the testing intervals. In chronically treated rats, endogenous extrasynaptosomal levels of both DA and NE were higher than in controls, while only NE was increased in the free fraction. These data are consistent with a morphine-induced increase in the biosynthesis of DA and NE, resulting in increased levels of NE in the nonfunctional storage pools rather than in the more readily available pools. This is supported by the lack of change in the levels of the bound fraction suggesting preferential release of newly synthesized NE followed by replenishment due to increased synthesis. These conditions could result in constant equilibration of the bound fraction.