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

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.