Chronic unpredictable restraint stress increases hippocampal pro-inflammatory cytokines and decreases motivated behavior in rats

Most chronic stress protocols are too laborious or do not abide by the two main characteristics of the stress concept: uncontrollability and unpredictability. The goal of this study was to establish a simple and reliable model of chronic stress, while maintaining the main features of the concept. Animals were exposed to chronic movement restraint with variable duration (2, 4 or 6 h, in an unpredictable schedule) for 3 weeks and assessed in several physiological and behavioral readouts known to reflect chronic stress states. Body weight, levels of plasma corticosterone, hippocampal pro-and anti-inflammatory cytokines, anxiety-like (novelty suppressed feeding and elevated plus maze) and motivated behaviors (sucrose negative contrast test and forced swim test) were evaluated three days after the end of the chronic protocol. Stressed animals had a lower body weight gain, higher levels of cytokines in the hippocampus, reduced suppression of a low concentration sucrose solution and increased immobility in the forced swim test. Based on these data, we suggest that chronic movement restraint with variable duration may be a suitable and simple protocol for the study of changes induced by chronic stress and for the testing of possible treatments relevant to psychiatry.