A COMPARATIVE-STUDY ON THE EFFECTS OF TETRACYCLINES AND LITHIUM ON THE CYCLIC-AMP 2ND-MESSENGER SYSTEM IN RAT-BRAIN

1. This study was aimed at investigating the effects of demeclocycline (DMC), minocycline (MC), and lithium (Li) in vitro on cyclic AMP (cAM P) accumulation in rat cerebral cortex stimulated by noradrenaline, fo rskolin, and ouabain. 2. DMC, MC, and Li dose-dependently reduced nora drenaline-stimulated cAMP formation in cortical slices, but only Li in hibited the cAMP formation induced by forskolin. 3. In contrast to Li, DMC and MC did not affect noradrenaline-stimulated adenylate cyclase activity in cortical membranes. 4. In cortical slices, ouabain stimula ted the cAMP production (required the presence of extracellular Ca2+ a nd was blocked by verapamil). Ouabain-stimulated cAMP accumulation in cortical slices was inhibited by DMC, MC, and Li. 5. DMC and MC do not seem to interact directly with the adenylate cyclase as reported for Li. It is concluded that the tetracyclines, DMC and MC, affect the cAM P signaling system in rat brain by mechanisms that differ from that of Li. The decreased receptor agonist-stimulated cAMP production in cort ical slices in the presence of DMC and MC may be due to the Ca2+-chela ting ability of these tetracyclines.