Serotonin and thermoregulation. Physiologic and pharmacologic aspects of control revealed by intravenous m-CPP in normal human subjects.
Meta-chlorophenylpiperazine (m-CPP), a probe of central serotonergic function, elevates core temperature in rodents, nonhuman primates, and humans via serotonin receptor-mediated mechanisms. To further characterize the thermoregulatory aspects of this response, we studied 16 healthy volunteers using multiple core and skin temperature recording sites. Compared to placebo, intravenous m-CPP (0.08 mg/kg) produced statistically significant biphasic changes in rectal temperature, characterized 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 effector mechanism primarily responsible for m-CPP-induced core hyperthermia is increased metabolic thermogenesis. Individual differences in the magnitude of the hyperthermia were independent of m-CPP plasma concentrations but were found to be linearly correlated with the level of the previous night's core rectal temperature minimum and mean. It appears that m-CPP activates a mode of metabolic thermogenesis governed by a nocturnally sensitive proportional control mechanism. The operation of such a proportional controller is characterized by a set point and a gain, and has been implicated in the general economy of mammalian energy balance.
Schwartz
P J
PJ
National Institute of Mental Health, Clinical Psychobiology Branch, Bethesda, MD 20892-1390, USA.
Wehr
T A
TA
Rosenthal
N E
NE
Bartko
J J
JJ
Oren
D A
DA
Luetke
C
C
Murphy
D L
DL
D000328:Adult; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010879:Piperazines / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
D010879:Piperazines; D017366:Serotonin Receptor Agonists; C015068:1-(3-chlorophenyl)piperazine; D009638:Norepinephrine