Effect of acute lipopolysaccharide administration on (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane-induced wet dog shake behavior in rats: comparison with body weight change and locomotor activity.

Abstract 1. Several reports have shown that serotonin (5-HT) 2A receptor density and its function are altered after physiological or pharmacological stress. To examine whether an acute administration of lipopolysaccharide (LPS), a bacterial endotoxin, affected 5-HT 2A receptor function, wet dog shakes of male Wistar rats were observed after a subcutaneous injection of DOI, a 5-HT 2A receptor agonist following LPS treatment. Body weight change and locomotor activity were also observed. 2. DOI (1 mg/kg)-induced WDS significantly decreased after 400 or 1000 μg/kg LPS treatment compared with that of control rats 1 and 3 hr after injection, and WDS completely recovered 8 hr after LPS treatment. Treatment with 10 mg/kg indomethacin (IND) or 1 mg/kg naltrexone (NLTX) canceled the effect of 400 μg/kg LPS on DOI-induced WDS. 3. Body weight decrease was significantly greater in LPS-treated rats compared with control rats 3, 5 and 8 hr after treatment. Treatment with IND (10 mg/kg) significantly recovered the reduction in body weight induced by 400 μg/kg LPS. Treatment with NLTX (1 mg/kg) also prevented the LPS effect on body weight decrease. 4. Eight hr after treatment with LPS (400 μg/kg), the rats showed significant attenuation of locomotor activity. IND (10mg/kg) treatment abolished the inhibitory effect of LPS on locomotor activity, and NLTX (1 mg/kg) also improved the decrease in locomotion 8 hr after LPS treatment. 5. Plasma tumor necrosis factor (TNF)-α concentration dramatically increased 1 hr after the injection of 400 μg/kg LPS, and returned almost to the basal level 3 hr later. Next, rats were injected with 50 μg/kg TNF-α intraperitoneally, and body weight change and DOI-induced WDS was determined 3 hr after TNF-α injection. Body weight loss was significantly greater in rats treated with TNF-α. On the other hand, DOI-induced WDS was not altered when rats were treated with TNF-α. 6. These results suggest that acute treatment with LPS inhibited 5-HT 2A receptor-mediated behavior via cyclooxygenase and opioid receptor activation, but that the inhibition of the WDS by LPS appears to be independent of TNF-α production.