Inhibition of noradrenaline stimulated increase in [Ca2+]i in cultured astrocytes by chronic treatment with a therapeutically relevant lithium concentration

Abstract

Chronic treatment of mouse astrocytes in primary cultures with 1 mM lithium chloride for 7-14 days decreased the basal level of free cytosolic calcium concentration ([Ca2+]i) from 50-70 nM to approximately 70% of this value and reduced the increase in [Ca2+]i caused by exposure to 1 microM noradrenaline (normally to 500-700 nM) by almost one half. A similar, but much smaller, response to serotonin was unaffected by chronic treatment with lithium. Acute exposure to lithium (30 min) had no effect on either basal or noradrenaline stimulated [Ca2+]i. The dependence on chronic, versus acute treatment suggests that this effect may be related to the therapeutic effect of lithium as a mood-stabilizing drug, which likewise requires chronic treatment. Since good evidence is found that noradrenaline increases [Ca2+]i by activation of the phosphoinositol second messenger system the present findings are also consistent with literature data that lithium acts by interfering with this system.