Chronic but not acute pharmacological activation of SERCA induces behavioral and neurochemical effects in male and female mice.

Chronic but not acute pharmacological activation of SERCA induces behavioral and neurochemical effects in male and female mice. Behav Brain Res. 2020 Oct 30;:112984 Authors: Britzolaki A, Cronin CC, Flaherty PR, Rufo RL, Pitychoutis PM Abstract Intracellular calcium (Ca2+) homeostasis is a vital process to nerve cell survival and function with an intricate regulatory network. It is well established that the endoplasmic reticulum (ER) is a major intraneuronal Ca2+ storage and that the sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) pump is a key regulator of cytosolic Ca2+ levels. SERCA pumps play a critical role in brain pathophysiology, thus SERCA comprises an emerging pharmacological target for the treatment of brain diseases. Interestingly, preclinical studies in rodents suggest that chronic pharmacological activation of SERCA2 by the quinoline derivative CDN1163 comprises a potential pharmacotherapeutic target in Alzheimer's and Parkinson's diseases. As little is known about the behavioral and neurochemical consequences of CDN1163 administration, in the current study we investigated the potential effects of acute (i.e., at 1 h) and chronic (i.e., 17 days) CDN1163 administration (i.e., 10 mg/kg and 20 mg/kg; intraperitoneally) on locomotor activity and relevant affective behaviors, as well as on monoaminergic neurotransmission in naïve C57BL/6 J mice of both sexes. Interestingly, chronic, but not acute, ...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research