Effects of acute and chronic morphine treatment of calmodulin activity of rat brain
Nehmad, R.; Nadler, H.; Simantov, R.
Molecular Pharmacology 22(2): 389-394
1982
ISSN/ISBN: 0026-895X PMID: 6128669 Document Number: 193009
The cAMP-phosphodiesterase assay was used to quantitate the amount of calmodulin activity in various brain areas of male rats treated acutely or chronically for 5 days with morphine. The acute treatment with morphine decreased calmodulin activity in the mitochondrial-synaptosomal P2 fraction of the striatum, midbrain and thalamus but had no effect on the cerebellum, which contains a low density of opiate receptors. The decrease in calmodulin activity by morphine was dose-dependent and was blocked by the opiate antagonist naloxone. Chronic treatment of rats with morphine increased calmodulin activity in the mitochondrial-synaptosomal P2 of the striatum, midbrain, cerebral cortex and thalamus. A highly sensitive Ca2+/Mg2+-ATPase assay was also used to quantitate the amount of calmodulin activity in subcellular fractions obtained from the striatum. Chronic morphine treatment caused a significant increase in calmodulin activity in the membrane containing microsomal, synaptosomal and mitochondrial layers but only a small change in the layer that contained the soluble proteins and the synaptic vesicles. Alteration of the content of calmodulin in specific subcellular sites may have a central role in opiate action and addiction via regulation of multiple calmodulin-sensitive biochemical pathways.