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

Abstract

The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na + ,K + -ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM) from cerebral cortex were prepared to determine Na + ,K + -ATPase activity. There was a significant decrease (10%) in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27%) in Na + ,K + -ATPase activity compared 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-dependent decrease in enzyme activity, with the maximal inhibition (60-80%) occurring at 0.5 mM. We suggest that a) imipramine might decrease Na + ,K + -ATPase activity by altering membrane fluidity, as previously proposed, and b) stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na + ,K + -ATPase activity is decreased in bipolar patients.

Maternal Depression Model: Long-Lasting Effects on the Mother Following Separation from Pups

“…-ATPase enzyme is an important feature of depression [13,46,47], and this reduction in the hippocampus has been observed in other animal models of depression [14,16,48]. Besides, treatment with antidepressants such as fluoxetine [49] and desipramine [50] has been reported to enhance Na ? , K ?…”

Fluoxetine and nortriptyline affect NTPDase and 5′-nucleotidase activities in rat blood serum

“…(10 mg/kg) of fluoxetine and nortriptyline 1 h before they were killed (Zanatta et al, 2001;Borelli et al, 2004;Ejsing and Linnet, 2005;Drapier et al, 2006). Control animals received saline injections (0.9% NaCl) in the same volume as those applied to antidepressant-treated rats.…”

“…The selection of this treatment was based on previous studies showing important neurochemical and antidepressant effects for both drugs (Silva and Brandão, 2000;Zanatta et al, 2001;Borelli et al, 2004;Bonanno et al, 2005;Gameiro et al, 2006). Control animals received saline injections (0.9% NaCl) in the same volume as those applied to antidepressants-treated rats.…”

“…Antidepressants were tested at final concentrations of 100, 250 and 500 μM (Dhalla et al, 1980;Zanatta et al, 2001).…”

Effect of repeated restraint stress and clomipramine on Na+/K+‐ATPase activity and behavior in rats

“…Na + /K + ‐ATPase is the enzyme responsible for the active transport of sodium and potassium ions in the nervous system, thus maintaining the ionic gradient necessary for neuronal excitability and regulation of neuronal cell volume. Its activity is decreased in patients with bipolar affective disorder and other psychiatric disorders such as depression (Zanatta et al, 2001). As a consequence, a decrease of Na + /K + ‐ATPase activity directly affects neurotransmitter signaling and neural activity, as well as the whole animal behavior (Jamme et al, 1995).…”