Endotoxin-induced reduction of social investigation by mice: interaction with amphetamine and anti-inflammatory drugs

Previous studies indicate that some aspects of endotoxin-induced sickness behavior in rats may be mediated by interleukin-1 stimulated events and can be attenuated by corticosteroids, cyclooxygenase inhibitors and the interleukin-1-receptor antagonist. In the current studies, we replicate and extend these findings in adult male mice. A relatively low dose of lipopolysaccharide (LPS; 15 mu g/kg, IP) was used to reliably induce a 50-60% reduction in the social investigation of a juvenile conspecific at 2-3 h after injection. Amphetamine (2.0-4.0 mg/kg, IP, 30 min pre-LPS) exacerbated LPS-induced decreases in investigation. Administration of methylprednisolone (10-30 mg/kg, IP), indomethacin (3-30 mg/kg, IP), and ibuprofen (1-l00 mg/kg, IP) 1 h before LPS significantly reduced LPS-induced sickness behavior at several doses. Dexamethasone (0.1-10 mg/kg, IP) partially antagonized sickness. Representative flavonoids rohitukine (0.01-100.0 mg/kg, IP) and chrysin (0.01-10 mg/kg, IP) also antagonized LPS-induced deficits in social investigation. These studies replicate and extend previous studies in rat to demonstrate systematic effects of low doses of LPS, antagonism by anti-inflammatory drugs and enhancement of LPS effects by amphetamine. The latter findings are consistent with a modulatory role for adrenergic activation on interleukin-1 release stimulated by endotoxicity.