Selective inhibition of thermogenesis by tributyl S,S,S,-phosphorotrithioate (DEF)

1 Rats and mice given tributyl S,S,S,-phosphorotrithioate (DEF) showed large dose-related falls in body temperature which lasted several hours to several days at environmental temperatures below thermoneutrality (30 to 31 degrees C). 2 DEF produced only mild sedation and a remarkable degree of motor control was retained even when body temperatures fell below 30 degrees C. At the dose producing maximal hypothermia only 2% of rats died within the first 24 h, although prolonged hypothermia was usually lethal. 3 Hypothermia was associated with a complete block of cold-induced thermogenesis, with relatively little effect on basal metabolism at thermoneutrality. 4 Heat conservation mechanisms (peripheral vasoconstriction and piloerection) appeared to be unaffected by DEF and retained their usual temperature thresholds. 5 Adrenal catecholamine secretion in response to handling or acute cold exposure was normal in DEF-treated rats but the fall in body temperature could be markedly reduced by large intraperitoneal injections of noradrenaline, although not atropine. The increase in oxygen consumption produced by injected catecholamines was also unaffected by DEF treatment. 6 It is concluded that the block of cold-induced thermogenesis probably results from a lack of catecholamine release at the tissue level. That this is likely to be mediated at a peripheral site is suggested by the lack of effect of intracerebroventricular DEF.