Aromatase Inhibition and Electroconvulsive Seizures in Adolescent Rats: Antidepressant and Long-Term Cognitive Sex Differences

Abstract

We recently showed sex differences in the antidepressant-like potential of electroconvulsive seizures (ECS) in adolescent rats; whereas it worked for male rats, it was inefficacious in females. Because sex steroids might be important modulators of these sex disparities, we evaluated the role of estrogens in the differential response induced by adolescent ECS. Moreover, given the literature suggesting certain cognitive sequelae from ECS exposure, we aimed at evaluating its long-term safety profile in adulthood. Adolescent Sprague-Dawley rats were pretreated with letrozole (1 mg/kg/day) or vehicle (1 mL/kg/day) for 8 days (i.p.) and treated during the last 5 days (3 hours later) with ECS (95 mA, 0.6 s, 100 Hz) or SHAM. Antidepressant-like responses were measured in the forced swim test, and long-term cognitive performance was assessed in the Barnes maze. During adolescence, whereas ECS alone exerted an antidepressant-like response in male rats, its combination with letrozole permitted ECS to also induce efficacy in females. Moreover, adolescent ECS treatment improved cognitive performance in adulthood although exclusively in male rats. Adolescent ECS demonstrated an antidepressant-like potential together with certain long-term beneficial cognitive effects but exclusively in male rats. For females, efficacy was restricted to a situation in which the biosynthesis of estrogens was reduced. Therefore, estrogens and/or testosterone levels play a crucial role in the sex disparities induced by ECS in Sprague-Dawley rats. Based on this study and on the literature supporting its safety, ECS should be encouraged for use in cases of treatment-resistant depression during adolescence, while adhering to sex-specific considerations.