||Constant exposure to light is prevalent in modern society where light noise, shift work, and jet lag is common. Constant light exposure disrupts circadian rhythm, induces stress and thus influences memory performance. We subjected adult male Wistar rats to a two-month exposure to constant light (LL), constant dark or normal light-dark cycles. Significant cognitive impairment and oxidative stress were observed in LL rats without a significant elevation in soluble Abeta1-42 levels. Next, we examined whether long-term exposure to constant light may accelerate dementia in a sub-pathological Abeta model of rats. Normal control rats received ACSF, AD rats received 440pmol, and sub-pathological Abeta rats (Abeta(s)) received 220pmol of human Abeta42 peptide in a single unilateral ICV administration. Sub-pathological Abeta rats exposed to constant light (LL+Abeta(s)) show significant memory deficits and oxidative damage, although not significantly different from LL rats. Additionally, constant light promoted aggregation of exogenous Abeta42 in LL+Abeta(s) rats shown by the presence of congophilic plaques. Furthermore, chronic fluoxetine treatment (5mg/kg/day) rescued rats from the behavioral deficits, oxidative damage and amyloid aggregation. Whereas, rifampicin treatment (20mg/kg/day) did not reverse the behavioral deficits or oxidative stress but rescued rats from amyloid plaque formation. It was concluded that constant light for two months induces behavioral deficits, oxidative stress, and accelerates aggregation of sub-pathological concentrations of human-Abeta42 peptides in Wistar rats, which is reversed by daily fluoxetine administration.