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

Abstract

Activation of the limbic-hypothalamic-pituitary-adrenal axis (LHPA) and the release of glucocorticoids are fundamental for the adaptive response and immediate survival of an organism in reaction to acute stimuli. However, high levels of glucocorticoids in the brain may produce neuronal injury and a decrease of Na(+)/K(+)-ATPase activity, with effects on neurotransmitter signaling, neural activity, as well as the whole animal behavior. Clomipramine is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine by indirect actions on the dopaminergic system and LHPA axis. Its chronic use increases the body's ability to cope with stress; however, high doses can potentiate its side effects on memory, learning, and sensory motor function. The purpose of the present study was to compare the effect of repeated restraint stress and clomipramine treatment on Na(+)/K(+)-ATPase activity and on the behavior of male rats. Changes in the behavioral response were evaluated by measuring the memory, learning, anxiety, and exploratory responses. Our results showed that exposure to repeated restraint stress reduced levels of Na(+)/K(+)-ATPase in brain structures and changed short and long-term memory, learning, and exploratory response when compared to the control group. Exposure to clomipramine treatment increased anxiety levels and reduced Na(+)/K(+)-ATPase activity in the cerebral cortex as well as short term memory, learning, and exploratory response. In conclusion, the present results provide additional evidence concerning how repeated restraint stress and clomipramine chronically administered at higher dose levels affect the neural activity and behavior of male rats.

The extent of involvement of ouabain, hippocampal expression of Na+/K+-ATPase, and corticosterone/melatonin receptors ratio in modifying stress-induced behavior differs according to the stressor in context

“…This offers a rationale for the ‘habituation' issue that might follow repeated restraints in rats, hindering behavioral responses. Unlike the upregulation of hippocampal CR in our study, the behavioral tolerance occurred parallel to reduced levels of hippocampal GR ( 27 ), indicating the bidirectional effects of stress - stimulated HPAA leading to either the occurrence or deficiency of stress responses ( 28 ), even though the effect of immobilization on body weight remains controversial, ranging from increase, to no change, to loss ( 29 ).…”