Abstract

The present work aimed to investigate the induction of circadian rhythm dysfunction and dementia upon chronic exposure to light-light and its reversal by melatonin in Wistar rats. Animals underwent different light-dark conditions, viz., light/dark (LD), light/light (LL), and dark/dark (DD) in respective groups for 4 months. Melatonin 0.5 mg/kg s.c., dextromethorphan 50 μg/100 g s.c., and mifepristone 25 μg/100 g s.c. were given once a day. Chronic LL and DD conditions significantly increased brain glutamate and cortisol levels. The LL period caused a deficit in spatial memory, working memory, decision making, and exploration of novel objects, compared to LD animals. A significant ( < 0.05) change in neuropathological observations in the hippocampus, CA1, CA2, and CA3; cortex; and cerebellum regions (40×, 100×, and 400×) was observed in the histological study. Induced oxidative stress in brain tissue was also observed by estimating tissue glutathione and TBARS levels. Dextromethorphan (NMDA antagonist), mifepristone (corticosterone antagonist), and melatonin significantly ( < 0.05) reversed the pathological states caused due to LL. The histological features in the hippocampus, cortex, and cerebellum region revealed inflammatory cells, vacuolation, and pyknotic cells, which were significantly rescued by antagonizing NMDA or cortisol or melatonin treatment. It may be concluded that continuous exposure to light-light conditions produced an imbalance between neuronal excitation and stress hormone, leading to poor cognitive abilities and neuropathology.