Abstract
Chronic stress induces sensorimotor, cognitive, and neuroendocrine alterations, particularly in females who exhibit heightened vulnerability to stress-related disorders. This study tested the hypothesis that chronic quetiapine administration during ongoing unpredictable chronic mild stress (UCMS) would attenuate stress-induced impairments in sensorimotor gating, recognition memory, and HPA-axis–related biochemical markers in female rats. Adult female Wistar rats were exposed to a 9-week UCMS paradigm, with quetiapine (10 mg/kg/day, i.p.) administered during the final 3 weeks. Behavioral outcomes were assessed using prepulse inhibition (PPI), startle reactivity, and the Novel Object Recognition (NOR) test. Serum and hippocampal corticosterone and BDNF levels were quantified by ELISA. Chronic stress significantly reduced PPI and recognition memory performance and increased serum and hippocampal corticosterone levels. Quetiapine treatment improved PPI and startle responsiveness, restored NOR discrimination index values, and partially attenuated stress-induced corticosterone elevations. Hippocampal BDNF levels were elevated in stressed animals and were modulated toward intermediate levels following quetiapine treatment. These findings indicate that chronic quetiapine administration mitigates behavioral and neuroendocrine alterations induced by prolonged stress in female rats. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11011-026-01834-8.