Psychotropic drugs attenuate lipopolysaccharide-induced hypothermia by altering hypothalamic levels of inflammatory mediators in rats

• Inflammation may contribute to the pathophysiology of mental disorders and psychotropic drugs are known to exert various effects on brain inflammation.
• Systemic administration of lipopolysaccharide (LPS) to rats causes robust production of inflammatory mediators and pathological changes in body temperature.
• Four psychotropic drugs significantly attenuated LPS-induced hypothermia in rats.
• Lithium, carbamazepine, haloperidol and imipramine differently affected levels of prostaglandin E2, tumor necrosis factor-α and phosphorylated p65 levels in plasma and hypothalamus of LPS-treated rats.

Recent evidence suggests that inflammation may contribute to the pathophysiology of mental disorders and that psychotropic drugs exert various effects on brain inflammation. The administration of bacterial endotoxin (lipopolysaccharide, LPS) to mammals is associated with robust production of inflammatory mediators and pathological changes in body temperature.The objective of the present study was to examine the effects of four different psychotropic drugs on LPS-induced hypothermia and production of prostaglandin (PG) E2, tumor necrosis factor (TNF)-α and phosphorylated-p65 (P-p65) levels in hypothalamus of LPS-treated rats.Rats were treated once daily with lithium (100 mg/kg), carbamazepine (40 mg/kg), haloperidol (2 mg/kg), imipramine (20 mg/kg) or vehicle (NaCl 0.9%) for 29 days. On day 29, rats were injected with LPS (1 mg/kg) or saline. At 1.5 h post LPS injection body temperature was measured, rats were sacrificed, blood was collected and their hypothalami were excised, homogenized and centrifuged. PGE2, TNF-α and nuclear P-p65 levels were determined by specific ELISA kits.We found that lithium, carbamazepine, haloperidol and imipramine significantly attenuated LPS-induced hypothermia, resembling the effect of classic anti-inflammatory drugs. Moreover, lithium, carbamazepine, haloperidol and imipramine differently but significantly affected the levels of PGE2, TNF-α and P-p65 in plasma and hypothalamus of LPS-treated rats.The results suggest that psychotropic drugs attenuate LPS-induced hypothermia by reducing hypothalamic production of inflammatory constituents, particularly PGE2. The effects of psychotropic drugs on brain inflammation may contribute to their therapeutic mechanism but also to their toxicological profile.