Sex differences in the effects of muramyl dipeptide and lipopolysaccharide on locomotor activity and the development of behavioral tolerance in rats

Administration of bacterial agents, such as muramyl dipeptide (MDP) or lipopolysaccharide (LPS), induces a number of illness symptoms including decreased locomotor activity and weight loss. This study provides a detailed multivariate assessment of the effects of repeated exposures of various doses of MDP and LPS, alone and in combination, on various aspects of locomotion in male and female rats. Animals were given a single intraperitoneal injection of either MDP (0.8 or 1.6 mg/kg), LPS (100 or 200 μg/kg), a combination of MDP and LPS (0.8 mg/kg and 100 μg/kg, respectively), or vehicle on Days 1, 4, and 7. Two hours after each injection, locomotor activity was recorded for 30 min in an automated open-field. Both doses of LPS and the high dose of MDP produced significant decrements in locomotor activity in male and female rats, with tolerance becoming evident over repeated administrations, although LPS decreased activity more robustly than MDP. Sex differences were evident in the combined effects of MDP and LPS. Together, MDP and LPS reduced male activity levels in an additive manner but significantly potentiated both horizontal and vertical activity decrements in females. In addition, the rate of behavioral tolerance development to repeated bacterial injections was significantly higher in females than in males. These findings provide evidence for sex differences in the actions of MDP and LPS on various aspects of locomotor activity and in the development of behavioral tolerance to infection.