Comparing the antidepressant-like effects of electroconvulsive seizures in adolescent and adult female rats: an intensity dose-response study

BackgroundThe induction of electroconvulsive seizures (ECS) in rodents induces sex- and age-specific disparities in antidepressant-like responses, with females and young age being the most unresponsive ones. Since the electrical charge needed to induce an effective convulsion is also altered by these variables, our aim was to compare different dose-intensities of ECS exclusively in female rats, since there is a lack of preclinical data characterizing this particular sex, while also evaluating efficacy during distinctive age periods of treatment (adolescence vs. adulthood).MethodsAdolescent and adult female Sprague-Dawley rats were exposed to an intensity dose-response study (55, 75 or 95 mA; 0.6 s, 100 Hz, 1 session/day, 5 days). The particular characteristics of the induced convulsions (tonic, clonic, recovery times) were monitored during treatment. Antidepressant-like responses were evaluated under the stress of the forced-swim test 1-, 3-, and 7-days post-treatment (i.e., improved immobility time as an indicative of an antidepressant-like response), and brains were collected 24 h later (8 days post-treatment) to evaluate potential changes in hippocampal neurogenesis (Ki-67 and NeuroD) by immunohistochemistry.ResultsThe lowest intensities tested of ECS (55 and 75 mA) induced an antidepressant-like effect in adult female rats, but rendered insufficient in adolescence. The lack of efficacy observed in adolescent rats paralleled differences in the characteristics of the seizures induced by ECS as compared to adulthood. In line with prior results, different dose-intensities of ECS modulated hippocampal neurogenesis in a comparable fashion with age (i.e., increased survival of neural progenitors 8 days post-treatment).ConclusionsIn conjunction, these results reinforce the importance of fine-tuning the parameters of ECS that might render efficacious while considering sex and age as essential variables for treatment response, and suggest that other molecular mechanisms, beside the partial role of hippocampal neurogenesis, might be participating in the antidepressant-like effects induced by ECS. Although the induction of electroconvulsive seizures (ECS) is a safe therapeutical option for treatment-resistant depression, there are important differences in treatment response driven by biological sex and age that require further characterization for ensuring optimal outcomes. In fact, most of the preclinical literature is centered in adult male rodents, with almost no prior studies characterizing ECS' response in adolescent female rodents. In this context, the present study compared the antidepressant-like responses induced by different intensity doses of ECS (55, 75 or 95 mA; 0.6 s, 100 Hz, 1 session/day, 5 days), exclusively in female rats (adolescent and adult). The results showed that the lowest doses tested (55 or 75 mA) induced an antidepressant-like response in adult female rats, while no dose was capable of inducing efficacy in adolescent female rats. These results replicated prior data from our group showing the inefficacy of the 95-mA dose at both ages, while demonstrating that lowering the dose is sufficient to exert efficacy in female adult rats. Further studies should center in adjusting the parameters to elicit efficacy in females during adolescence. There are clear sex and age differences in the antidepressant-like effects of ECS.Low dose intensities of ECS exerted antidepressant-like effects in adult female rats.ECS, at the doses tested, did not induce behavioral changes in adolescent female rats.ECS increased neurogenesis independently of the dose and age of treatment.

Automated summary

Low dose intensities of ECS exerted antidepressant-like effects in adult female rats. ECS, at the doses tested, did not induce behavioral changes in adolescent female rats. ECS increased neurogenesis independently of the dose and age of treatment.