Evaluation of Cerebral Microcirculation and Behavioral Responses in a Model of Chronic Social Stress Treated with Piperine

Chronic social stress is one of the most prevalent forms of stress in modern life and may induce behavioral alterations, such as increased aggressiveness, as well as changes in cerebral microcirculation. Piperine has antioxidant properties and may act as a neuroprotective agent and regulator of blood flow. The aim of this study was to evaluate cerebral microcirculation in animals subjected to chronic social stress, with or without piperine treatment. Chronic social stress was induced using the Spontaneous Aggressiveness Model, and animals were classified into three categories: harmonic (Har; positive control), aggressor (AgR), and defeated (AgD). A group was not exposed to chronic social stress (negative control). Cerebral microcirculation was assessed by quantifying functional and non-functional capillary densities and measuring cerebral blood flow using intravital microscopy and laser speckle imaging, respectively. Piperine was administered orally one day after stress exposure. AgR animals exhibited a reduction in functional capillary (201.2 ± 12.86 capillaries/mm²; p ≤ 0.05) and an increase in non-functional capillary density (17.40 ± 3.27 capillaries/mm²; p ≤ 0.01). Both AgD and AgR animals showed increased cerebral blood flow (186.1±8.3, p≤0.05; and 195.1± 9.6, p ≤ 0.01, respectively). Following piperine treatment, the number of harmonic animals increased from 32 to 42, whereas the numbers of AgD and AgR animals decreased to 5 and 2, respectively (control values: AgD = 10; AgR = 8). Preliminary results showed no statistically significant differences in functional or non-functional capillary densities after piperine treatment. However, piperine treatment reduced the development of aggressive behavior and promoted resilience in animals exposed to chronic social stress. These findings suggest that piperine may exert beneficial effects on behavioral responses to chronic social stress, although its effects on cerebral microcirculation require further investigation.