Effect of aerobic exercise on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine and to ipsapirone in untrained healthy subjects

Psychopharmacology (Berl). 2001 May;155(3):234-41. doi: 10.1007/s002130100706.


Rationale: Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise.

Objectives: The present study examines the effects of a 10-week protocol of moderate aerobic exercise (3-4 miles jogging 3 times per week) on central serotonergic receptor sensitivity.

Methods: Neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP; 0.4 mg/kg), ipsapirone (0.3 mg/kg), and placebo were performed in 12 untrained healthy volunteers before and after 10 weeks of moderate aerobic exercise.

Results: Before training, administration of the non-selective serotonergic agonist m-CPP, which exerts a number of well-reproducible effects mainly via its action on 5-HT2C receptors, was associated with a significant increase of cortisol and prolactin (but not adrenaline or noradrenaline) in comparison with the placebo condition. After the 10-week training period, administration of m-CPP was followed by a blunted cortisol response which was not significantly increased in comparison to the placebo challenge. In contrast, the increases of cortisol observed after administration of the 5-HT1A agonist ipsapirone were of the same magnitude during the pre- and post-training challenge sessions. The behavioral response to ipsapirone and the mean maximal increases of plasma adrenaline and noradrenaline did not change during the training period.

Conclusions: Regular aerobic exercise is associated with a blunted cortisol response to m-CPP, which might reflect a downregulation of central 5-HT2C receptors.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Behavior / drug effects*
  • Behavior / physiology*
  • Double-Blind Method
  • Down-Regulation / drug effects
  • Exercise / psychology*
  • Exercise Test
  • Female
  • Humans
  • Hydrocortisone / blood
  • Jogging / psychology*
  • Male
  • Neurosecretory Systems / drug effects*
  • Neurosecretory Systems / physiology*
  • Panic / drug effects
  • Piperazines / blood
  • Piperazines / pharmacology*
  • Prolactin / blood
  • Pyrimidines / blood
  • Pyrimidines / pharmacology*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists / blood
  • Serotonin Receptor Agonists / pharmacology*


  • Piperazines
  • Pyrimidines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • ipsapirone
  • Prolactin
  • 1-(3-chlorophenyl)piperazine
  • Hydrocortisone