Neural substrate of cold‐seeking behavior in endotoxin shock

Involvement of hypothalamic structures, viz., the preoptic area (POA), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH), in thermoregulatory behaviors associated with endotoxin (lipopolysaccharide, LPS)‐induced systemic inflammation was studied in rats. The rats were allowed to select their thermal environment by freely moving in a thermogradient apparatus. A low intravenous dose of E. coli LPS (10 μg/kg) caused warmth‐seeking behavior, whereas a high, shock‐inducing dose (5,000 μg/kg) caused cold seeking. Bilateral electrocoagulation of the PVH or DMH, but not of the POA, prevented this cold‐seeking response. Lesioning the DMH with ibotenic acid, an excitotoxin that destroys neuronal bodies but spares fibers of passage, also prevented LPS‐induced cold‐seeking behavior; lesioning the PVH with ibotenate did not affect it. Lesions of no structure affected cold‐seeking behavior induced by heat exposure or by pharmacological stimulation of the transient receptor potential (TRP) vanilloid‐1 (“warmth receptor”). Nor did any lesion affect warmth‐seeking behavior induced by a low dose of LPS, cold exposure, or pharmacological stimulation of the TRP melastatin‐8 channel (“cold receptor”). In conclusion, LPS‐induced cold‐seeking response is mediated by neuronal bodies located in the DMH and neural fibers passing through the PVH.