SEROTONIN AND THERMOREGULATION - PHYSIOLOGICAL AND PHARMACOLOGICAL ASPECTS OF CONTROL REVEALED BY INTRAVENOUS M-CPP IN NORMAL HUMAN-SUBJECTS

Meta-chlorophenylpiperazine (m-CPP), a probe of central serotonergic f unction, elevates core temperature in rodents, nonhuman primates, and humans via serotonin receptor-mediated mechanisms. To further characte rize the thermoregulatory aspects of this response, we studied 16 heal thy volunteers using multiple core and skin temperature recording site s. Compared to placebo, intravenous m-CPP (0.08 mg/kg) produced statis tically significant biphasic changes in rectal temperature, characteri zed by initial hypothermia (-0.04 degrees C at 12 minutes) followed by progressive hyperthermia (+0.17 degrees C at 90 minutes). m-CPP also produced significant increases in plasma norepinephrine concentrations . Analysis of the skin temperature recordings suggests that the effect or mechanism primarily responsible for m-CPP-induced care hyperthermia is increased metabolic thermogenesis. Individual differences in the m agnitude of the hyperthermia were independent of m-CPP plasma concentr ations but were found to be linearly correlated with the level of the previous night's core rectal temperature minimum and mean. If appears that m-CPP activates a mode of metabolic thermogenesis governed by a n octurnally sensitive proportional control mechanism. The operation of suck a proportional controller is characterized by a set point and a g ain, and has been implicated in the general economy of mammalian energ y balance.