LI-YU CHEN2026-10-162026-10-162015-12-17Pure ID: 15463265Pure UUID: 08489f66-b3eb-4b5a-a0e7-234780eec45810.1038/srep18420https://www.scopus.com/pages/publications/84950315772https://scholars.csmu.edu.tw/handle/123456789/25415Excessive exposure to club drug (GHB) would cause cognitive dysfunction in which impaired hippocampal Ca 2+ -mediated neuroplasticity may correlate with this deficiency. However, the potential changes of in vivo Ca 2+ together with molecular machinery engaged in GHB-induced cognitive dysfunction has never been reported. This study aims to determine these changes in bio-energetic level through ionic imaging, spectrometric, biochemical, morphological, as well as behavioral approaches. Adolescent rats subjected to GHB were processed for TOF-SIMS, immunohistochemistry, biochemical assay, together with Morris water maze to detect the ionic, molecular, neurochemical, and behavioral changes of GHB-induced cognitive dysfunction, respectively. Extent of oxidative stress and bio-energetics were assessed by levels of lipid peroxidation, Na + /K + ATPase, cytochrome oxidase, and [ 14 C]-2-deoxyglucose activity. Results indicated that in GHB intoxicated rats, decreased Ca 2+ imaging and reduced NMDAR1, nNOS, and p-CREB reactivities were detected in hippocampus. Depressed Ca 2+ -mediated signaling corresponded well with intense oxidative stress, diminished Na + /K + ATPase, reduced COX, and decreased 2-DG activity, which all contributes to the development of cognitive deficiency. As impaired Ca 2+ -mediated signaling and oxidative stress significantly contribute to GHB-induced cognitive dysfunction, delivering agent(s) that improves hippocampal bio-energetics may thus serve as a promising strategy to counteract the club drug-induced cognitive dysfunction emerging in our society nowadays.enjournal article