Mechanism of lithium action: in vivo and in vitro effects of alkali metals on brain superoxide dismutase.

Intraperitoneal administration of lithium (2 mEq/kg/day) was found to increase the superoxide dismutase (SOD) activity in certain brain regions after 24 hours (2 injections) and 3 days (once a day) of exposure. In vitro addition of wide range of lithium (0.1 to 8 mEq) to enzyme preparation as well activated cortical SOD activity; however, at 10 mEq concentrations an inhibition was observed. The increase in SOD activity did not appear to be region specific as under both in vivo and in vitro conditions lithium enhanced enzyme activity in all the tested brain regions. The effects of intraperitoneal administration of 2 mEq/kg rubidium and cesium for 24 hr (2 injections) and 6 days (once a day) were also studied on central SOD. Both the alkali metals were not found to produce any significant alteration in the cortical enzymic activity. When the in vitro effects of these monovalent alkali metals were tested, only 2 mEq rubidium was found to increase cortical SOD; however, cesium and potassium at similar concentration did not produce any appreciable effects. It appears from the data that lithium-induced increase in brain SOD activity is not an unspecific effect of alkali metals. SOD enzyme disposes cytotoxic superoxide radicals which, if not removed, could impair the normal functioning of cellular membrane and produce a variety of psychedelic compounds as well. The activation of central SOD by lithium would enhance the disposal process of superoxide radicals whose pathological concentrations may be present in affective disorders. The mechanism of lithium-induced activation of SOD, at present, is not known.