Sex differences in the antidepressant-like potential of repeated electroconvulsive seizures in adolescent and adult rats: Regulation of the early stages of hippocampal neurogenesis

Abstract

Age and sex are critical factors for the diagnosis and treatment of major depression, since there is a well-known age-by-sex difference in the prevalence of major depression (being females the most vulnerable ones) and in antidepressant efficacy (being adolescence a less responsive period than adulthood). Although the induction of electroconvulsive seizures (ECS) is a very old technique in humans, there is not much evidence reporting sex- and age-specific aspects of this treatment. The present study evaluated the antidepressant- and neurogenic-like potential of repeated ECS across time in adolescent and adult rats (naïve or in a model of early life stress capable of mimicking a pro-depressive phenotype), while including a sex perspective. The main results demonstrated age- and sex-specific differences in the antidepressant-like potential of repeated ECS, since it worked when administered during adolescence or adulthood in male rats (although with a shorter length in adolescence), while in females rendered deleterious during adolescence and ineffective in adulthood. Yet, repeated ECS increased cell proliferation and vastly boosted young neuronal survival in a time-dependent manner for both sexes and independently of age. Moreover, pharmacological inhibition of basal cell proliferation prevented the antidepressant-like effect induced by repeated ECS in male rats, but only partially blocked the very robust increase in the initial cell markers of hippocampal neurogenesis. Overall, the present results suggest that the induction of the early phases of neurogenesis by ECS, besides having a role in mediating its antidepressant-like effect, might participate in some other neuroplastic actions, opening the path for future studies.