VALPROIC ACID DIFFERS IN ITS IN-VITRO EFFECT ON GLUTAMIC-ACID DECARBOXYLASE ACTIVITY IN NEONATAL AND ADULT-RAT BRAIN

1. The in vitro effect of valproic acid (VA) (10(-6) to 10(-3) M) on g lutamic acid decarboxylase (GAD) activity in whole brain and cerebral cortex (CC) of neonates and of adult rats was examined. 2. VA did not induce changes on GAD activity either in CC or in the rest of the brai n (RB) of adult animals. 3. But at 10(-3) M, VA induced an increase in GAD activity in homogenates of non cortical brain areas of neonates; no increments were found in CC of these animals. This latter increase was detected in the membrane bound fraction of the enzyme and was not due to physicochemical nonspecific changes related to the potential so lvent activity of VA at this high concentration. 4. We may conclude th at VA induces changes on GAD activity in neonatal stages of developmen t but not in adult brain. Therefore, although a direct enhancement of GAD activity may play a role in the mechanism of action of VA in pedia tric patients, this cannot be verified in the adult population.