Serotonin and thermoregulation. Physiologic and pharmacologic aspects of control revealed by intravenous m-CPP in normal human subjects

Neuropsychopharmacology. 1995 Oct;13(2):105-15. doi: 10.1016/0893-133X(95)00026-A.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Body Temperature / drug effects*
  • Body Temperature Regulation / physiology*
  • Female
  • Humans
  • Male
  • Norepinephrine / blood
  • Piperazines / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • Time Factors


  • Piperazines
  • Serotonin Receptor Agonists
  • 1-(3-chlorophenyl)piperazine
  • Norepinephrine