EFFECTS OF CHRONIC TREATMENT WITH VALPROATE ON SEROTONIN-1A RECEPTOR-BINDING AND FUNCTION

Valproate is effective in treating bipolar disorder characterized by r apid cycling or acute mania, although the mechanism of action is uncle ar. In contrast to other treatments for depression, 21 days of treatme nt in rats with valproate (100, 200 or 400 mg/kg) did not significantl y alter the hypothermia induced by 8-hydroxy-2-(di-n-propyl)aminotetra lin (8-OH-DPAT), an agonist at serotonin-1A receptors. Treatment with valproate also had no effect on radioligand binding to serotonin-1A, s erotonin-2 or beta-adrenergic receptors. Based on these animal studies in frontal cortex and hippocampus, the therapeutic benefit of valproa te in mood disorders does not appear to involve adaptive changes in se rotonin-1A, serotonin-2 or beta-adrenergic receptor number.