EFFECTS OF MINOCYCLINE ON ACCUMULATION OF CYCLIC-AMP IN CEREBRAL-CORTEX OF RAT - A COMPARISON WITH LITHIUM

The tetracycline minocycline and lithium have been reported to share s ome biochemical properties. This study was aimed at investigating the effects of minocycline and lithium in vitro on accumulation of noradre naline-, forskolin- and calcium-(Ca2+) stimulated cyclic AMP (cAMP) in the cerebral cortex of the rat. Minocycline and lithium dose-dependen tly inhibited noradrenaline-stimulated formation of cAMP in slices of cortex, but only lithium inhibited the formation of cAMP induced by fo rskolin. In contrast to lithium, minocycline did not affect either nor adrenaline- or Ca2+-stimulated activity of adenylate cyclase in a prep aration of cortical membranes. However, in slices of cortex ouabain-in duced formation of cAMP (dependent on extracellular Ca2+ and blocked b y the Ca2+ channel antagonist, verapamil) was reduced both by minocycl ine and lithium. The present results indicate that the mechanisms of a ction of minocycline and lithium on the cAMP signalling system in the brain of the rat differ. Minocycline does not seem to interact directl y with the adenylate cyclase, as reported for lithium. The decreased a gonist-stimulated production of cAMP in intact cells, in the presence of minocycline, might be due to the ability of minocycline to chelate Ca2+ ions.