ETHANOL, SEROTONIN METABOLISM, AND BODY TEMPERATURE*

Abstract

The clinical effect of ethanol on temperature in humans is well known.Heavy drinking has been shown to lower body temperature, I and severe withdrawal symptomatology includes hyperthermia as a characteristic complicating feature.* Victor3 reported that patients dying during delirium tremens were in a state of hyperthermia, even when no concommitant infection, illness, or injury could be discerned.The underlying physiologic or biochemical mechanism of action of ethanol on central nervous system (CNS) mediated temperature regulation is unknown.Recently, several model systems for inducing withdrawal symptoms in rodents (mice and rats) have been d e v e l ~p e d .~~~ However, the effects of chronic ethanol administration on temperature regulation in such animals have not been studied.CNS serotonergic systems have been postulated to be involved with the control of body temperature in rodents.In addition, the deaminated metabolites of serotonin (e.g., 5-hydroxytryptophol) have also been hypothesized to regulate temperature in the mouse.'Previous studies from our laboratory have shown that either a single dose or chronic administration of ethanol produces an increase in the levels of serotonin metabolites in the brainx and that this increase after a single dose of ethanol is due to the inhibition of transport systems for these metabolites (e.g., 5-hydroxyindoleacetic acid) out of the brain.9Thus, it was of interest to determine whether direct application of serotonin, other biogenic amines, or their metabolites into the CNS affected body temperature in the mouse and how ethanol interacted with such effects. MATERIALS A N D METHODSC57B1/6J mice (Jackson Laboratories) were housed in our laboratories for a minimum of 7 days before use in these studies.Before use, the mice were kept at 21-24" c with a 6 AM-6 PM light cycle.Only male mice 20-25 g in weight (60-80 days of age) were used in these studies.Mice, unless otherwise indicated, were allowed ad lib.access to water and Purina Lab Chow@.Serotonin creatinine sulfate (5-HT), 5hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), and dopamine (DA) were obtained from Sigma Chemical Company.5-Hydroxytryptophol (5-HTOL), vanillylmandelic acid (VMA), and homovanillic acid (HVA) were obtained from Regis Chemical Company.