Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

Abstract Background Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic–pituitary–adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar–Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). Objective The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1 day) and at a longer delay (7 days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Methods Male Wistar and WKY rats received 5 days of repeated ECS or sham treatment and were assessed 1 and 7 days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Results Both strains showed the expected antidepressant response and retrograde memory impairments at 1 day following ECS, which were sustained at 7 days. In addition, at 1 day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7 days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. Conclusions The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT.