LITHIUM EXERTS A TIME-DEPENDENT AND TISSUE-SELECTIVE ATTENUATION OF THE DEXAMETHASONE-INDUCED POLYAMINE RESPONSE IN RAT-BRAIN AND LIVER

It has previously been shown that chronic, but not acute, lithium trea tment indirectly prevents the dexamethasone-induced increase in brain polyamine-metabolizing enzymes. In the present study we determined the effects of lithium treatment on changes in cellular polyamines, 6 h a fter dexamethasone challenge (3 mg/kg intraperitoneally). The findings demonstrate that chronic lithium (daily intraperitoneal 2.5 mmol/kg i njections for 2 weeks) treatment completely prevents the accumulation of putrescine, in parallel to its prevention of the dexamethasone-indu ced increase in ornithine decarboxylase activity. A partial attenuatio n of this polyamine response was also observed in the liver. Only mino r and inconsistent changes were observed in the concentrations of the polyamines, spermidine and spermine. Acute lithium treatment (a single injection at times ranging from 1 to 24 h prior to dexamethasone chal lenge) did not attenuate the dexamethasone-induced increases in brain putrescine concentration nor in ornithine decarboxylase activity. It i s suggested that prevention of the stress-induced polyamine response i n the brain may be an important mechanism through which prophylactic l ithium may exert its beneficial effect in manic-depressive illness.