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

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 70% of this value and reduced the increase in Ca²⁺]_i caused by exposure to 1 μM 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.