Effect of Piperine on Brain Leukocyte Rolling and Adhesion on Animal Model of Chronic Social Stress

Chronic stress is a major risk factor for neurobiological and behavioral alterations, including psychiatric disorders such as depression and anxiety. Social stress, motivated by interpersonal relations, is prevalent in urban environments, and can contribute to the establishment of stress-related homeostasis disruption, which includes neuroinflammation. Piperine, an alkaloid extracted from Piper nigrum, has demonstrated anti-inflammatory and neuroprotective effects, including the capacity to suppress central cytokine levels and improve depression-like behavioral alterations in preclinical models. Therefore, we investigated piperine as a therapeutic agent to alleviate the neuroinflammatory effects of chronic social stress in the Model of Spontaneous Aggression (MSA). Swiss Webster mice were grouped at three weeks of age. At week 10, animals were either maintained non-regrouped (NR) or regrouped based on mobility profiles assessed by the tail suspension test. Behavioral tests performed every two weeks categorized regrouped individuals as attacked (AgD), aggressive (AgR), or harmonic (Har). The treated group received piperine (15 mg/kg, p.o.) for six weeks post-regrouping, while controls received water. Leukocytes in the cerebral circulation were visualized via intravital microscopy. The Pattern of Aggressive Behavior and Ethogram tests showed that piperine treatment led to a significant reduction in the number of both AgD and AgR animals and an increase in Har individuals, as well as a reduction in lesion extension. AgD mice showed enhanced leukocyte rolling and adhesion in the cerebral cortex compared to NR, which our preliminary results indicate piperine was unable to prevent. In conclusion, although piperine effectively modulates aggressive behavioral outcomes under chronic social stress, its effects on specific neuroinflammatory pathways require further elucidation.