Neural substrate of cold-seeking behavior in endotoxin shock.
Systemic inflammation is a leading cause of hospital death. Mild systemic inflammation is accompanied by warmth-seeking behavior (and fever), whereas severe inflammation is associated with cold-seeking behavior (and hypothermia). Both behaviors are adaptive. Which brain structures mediate which behavior is unknown. The involvement of hypothalamic structures, namely, the preoptic area (POA), paraventricular nucleus (PVH), or 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 Escherichia coli LPS (10 microg/kg) caused warmth-seeking behavior, whereas a high, shock-inducing dose (5,000 microg/kg) caused cold-seeking behavior. 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. Lesion of no structure affected cold-seeking behavior induced by heat exposure or by pharmacological stimulation of the transient receptor potential (TRP) vanilloid-1 channel ("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 ("cold receptor"). We conclude that LPS-induced cold-seeking response is mediated by neuronal bodies located in the DMH and neural fibers passing through the PVH. These are the first two landmarks on the map of the circuitry of cold-seeking behavior associated with endotoxin shock.
Almeida
Maria C
MC
Systemic Inflammation Laboratory, Trauma Research, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States of America; Medical School of Ribeirão Preto, São Paulo, Brazil.
Steiner
Alexandre A
AA
Branco
Luiz G S
LG
Romanovsky
Andrej A
AA
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000293:injuries / Q000473:pathology / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D011301:Preoptic Area / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology
D008070:Lipopolysaccharides