BRAIN POLYAMINE STRESS-RESPONSE - RECURRENCE AFTER REPETITIVE STRESSOR AND INHIBITION BY LITHIUM

We recently demonstrated that, unlike in peripheral tissues, the incre ase in activity of polyamine synthesizing enzymes observed in the brai n after acute stress can be prevented by long-term, but not by short-t erm, treatment with lithium. In the present study we sought to examine the effects of chronic intermittent stress on two key polyamine synth esizing enzymes, ornithine decarboxylase and S-adenosylmethionine deca rboxylase, and their modulation by lithium treatment. Adult male rats were subjected to 2 h of restraint stress once daily for 5 days and to an additional delayed stress episode 7 days later. Enzyme activities were assayed 6 h after the beginning of each stress episode. in contra st to the liver, where ornithine decarboxylase activity was increased (300% of the control) only after the first stress episode, the enzyme activity in the brain was increased after each stress episode (to simi lar to 170% of the control). Unlike ornithine decarboxylase activity, S-adenosylmethionine decarboxylase activity was slightly reduced after the first episode (86% of the control) but remained unchanged thereaf ter. After cessation of the intermittent stress period, an additional stress episode 7 days later led again to an increase in ornithine deca rboxylase activity in the brain (225% of the control) but not in the l iver, whereas S-adenosylmethionine decarboxylase activity remained unc hanged. The latter increase in ornithine decarboxylase activity was bl ocked by lithium treatment during the intervening 7-day interval betwe en stressors. The results warrant the following conclusions: (a) Repet itive application of stressors results in a recurrent increase in orni thine decarboxylase activity in the brain but to habituation of this r esponse in the liver. (b) This brain polyamine stress response can be blocked by long-term (days) lithium treatment. (c) The study implicate s an overreactive polyamine response as a component of the adaptive, o r maladaptive, brain response to stressful events and as a novel molec ular target for lithium action.