TEMPORAL DYNAMICS OF COGNITIVE AND NON-COGNITIVE BEHAVIORAL PHENOTYPES IN THE ICV-STZ RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE

Intracerebroventricular streptozotocin (ICV-STZ, 3 mg/kg) is a widely used non-transgenic model of sporadic Alzheimer’s disease (sAD), yet its early cognitive and non-cognitive dynamics remain incompletely characterized. In a cross-sectional design, we assessed pain-related signs, peripheral glycemia, locomotor activity, and memory phenotypes in three independent cohorts of male Wistar rats at 5-7, 43-45, and 88-90 days post-injection. ICV-STZ induced transient pain-like behavior (Rat Grimace Scale scores 1.0-4.0, days 1-14), persistent body-weight deficit, and normal peripheral glycemia, consistent with central insulin resistance without systemic metabolic toxicity. Open-field testing revealed a tri-phasic pattern: reduced rearing at 5 days (p < 0.0001), selective hyperactivity (increased mean/maximum speed, p < 0.05) at 43 days with preserved total distance traveled, and increased immobility at 88 days (p = 0.036). Hippocampal-dependent short-term spatial memory (novel object location task) showed a non-significant trend toward reduced discrimination indices across time points (treatment main effect, p = 0.078). In contrast, perirhinal-dependent long-term object recognition memory (novel object recognition task, NOR) was impaired at 7 days (p = 0.033) and 90 days (p = 0.037) but preserved at 45 days (p = 0.915). Early NOR impairment correlated with reduced rearing (r = 0.469, p = 0.049), suggesting that acute discomfort negatively influences exploratory-driven cognitive performance. Preservation of NOR at 45 days coincided with increased object exploration. These findings reveal novel temporal dynamics in the ICV-STZ model, including pain-related modulation of early cognitive outcomes and a ~45-day window of behavioral compensation, providing a framework for targeted interventions in sAD.