In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats

The effects of in vivo chronic treatment and in vitro addition of imipramin e, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptak e inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were stu died. Adult Wistar rats received daily intraperitoneal injections of 10 mg/ kg of imipramine or fluoxetine for 14 days. Twelve hours after the last inj ection rats were decapitated and synaptic plasma membranes (SPM) from cereb ral cortex were prepared to determine Na+,K+-ATPase activity. There was a s ignificant decrease (10%) in enzyme activity after imipramine but fluoxetin e treatment caused a significant increase (27%) in Na+,K+-ATPase activity c ompared to control (P <0.05, ANOVA; N = 7 for each group). When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-depend ent decrease in enzyme activity, with the maximal inhibition (60-80%) occur ring at 0.5 mM. We suggest that a) imipramine might decrease Na+K+-ATPase a ctivity by altering membrane fluidity, as previously proposed, and b) stimu lation of this enzyme might contribute to the therapeutic efficacy of fluox etine, since brain Na+,K+-ATPase activity is decreased in bipolar patients.