Neutralization of endogenous digitalis-like compounds alters catecholamines metabolism in the brain and elicits anti-depressive behavior

Depressive disorders are among the world's greatest public health problems. Na ⁺, K ⁺-ATPase is the established receptor for the steroidal digitalis-like compounds (DLC). Alteration in brain Na ⁺, K ⁺-ATPase and DLC have been detected in depressive disorders raising the hypothesis of their involvement in these pathology. The present study was designed to further elaborate this hypothesis by investigating the behavioral and biochemical consequences of neutralization in brain DLC activity attained by anti-ouabain antibodies administrations, in normal Sprague-Dawley (SD) and in the Flinders Sensitive Line (FSL) of genetically depressed rats. Chronic i.c.v. administration of anti-ouabain antibodies to FSL rats elicited anti-depressive behavior. Administration of anti-ouabain antibodies intracerebroventriculary (i.c.v.) to SD rats significantly changed the levels of catecholamines and their metabolites in the hippocampus, ventral tegmentum and nucleus accumbence. These results are in accordance with the notion that endogenous DLC may be involved in the manifestation of depressive disorders and suggests that alteration in their levels may be of significant therapeutic value.