Decreased Neuroendocrine Responses to Meta-Chlorophenylpiperazine (m-CPP) but Normal Responses to Ipsapirone in Marathon Runners

Abstract

Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise. To study the effects of exercise on central serotonergic receptor sensitivity, we performed neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP, 0.4 mg/ kg), ipsapirone (0.3 mg/kg) and placebo in 12 marathon runners and 12 healthy controls not practicing regular exercise. After administration of the nonselective serotonergic agonist m-CPP, which exerts a number of wellreproducible effects mainly by means of its action on 5-HT Meta-chlorophenylpiperazine (m-CPP); Ipsapirone Several studies of healthy volunteers have shown a positive effect of endurance training on anxiety, depressive symptoms, self-esteem, concentration, sexual satisfaction, and stress tolerance (de Coverley Veale 1987;Farmer et al. 1988;Hughes 1984;Lennox et al. 1990;MacMahon 1990;Sothman et al. 1992). There is also some evidence that exercise is effective against mild-to-moderate depression and against anxiety disorders (Doyne et al. 1987;Greist et al. 1979;Martinsen et al. 1985;McCann and Holmes 1984;Pappas et al. 1990;Sexton et al. 1989). Research in sports medicine has focused on physiological and immunological consequences of exercise, and little is known about changes in central neurotransmitter function associated with acute or regular endurance training.Several lines of evidence suggest that motor activity affects central serotonin metabolism. In the cerebrospinal fluid of depressed patients, the concentration of the serotonin metabolite 5-HIAA was significantly higher after 4 hours of motor activity than in the same patients after bed rest (Post et al. 1973). Aerobic exercise causes a rise of free fatty acids Fischer et al. From the Department of Psychiatry, University of Göttingen, Göt-tingen, Germany (AB, DM, BB, GH, UB, ER), the Department of Neurology (AG), University of Würzburg, Würzburg, Germany; the Department of Clinical Pharmacology (CHG), Department of Sports Medicine (UH-V), University of Göttingen, Göttingen, Germany; Institute of Sports and Preventive Medicine (TM), University of Saarbrücken, Saarbrücken, Germany.Address correspondence to: Dr. A. Broocks, The Department of Psychiatry, University of Göttingen, von-Siebold-Strasse 5, D-37075 Göttingen, Germany.Received 28 October 1997; revised 12 March 1998; accepted 13 April 1998. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 2 Decreased Serotonergic Responsiveness in Marathon Runners 151 1991), which displace free tryptophan (TRP) from its plasma-protein-binding sites (Blomstrand et al. 1988;Chaouloff et al. 1986). This leads to an increase of free TRP in relation to other large neutral amino acids (LNAA) (Chaouloff et al. 1989). Because the TRP influx into the brain correlates with the TRP/LNAA plasma ratio (Fernstrom and Wurtman 1971;Wurtman and Fernstrom 1976), exercise leads to a higher precursor availability in the brain, which, in turn, stimulates 5-HT synthesis (Broocks et al. 1989;Chaouloff 1997). Data from animal studies show th...

Exercise-Associated Changes in the Corticosterone Response to Acute Restraint Stress: Evidence for Increased Adrenal Sensitivity and Reduced Corticosterone Response Duration

“…Rodents with wheel access typically show a more finely tuned response to stressors, mounting a more robust response than sedentary animals to those with physical components such as forced swim or restraint that would demand sufficient mobilization of energy resources (Campbell et al, 2009;Droste et al, 2007;Droste et al, 2003;Droste et al, 2006), and a more curtailed response to those that are purely psychogenic, such as loud noise or novel cage exposure that would require less energy Droste et al, 2007;Droste et al, 2003). A similar finding is observed in humans in that exercise blunts the HPA-axis response to a single exposure of oral mCPP a 5HT-2C agonist with anxiogenic properties (Broocks et al, 1999;Broocks et al, 2001). Taken together, these findings suggest that exercise may improve control over the HPA-axis response to stress, producing a more efficient response that is enhanced or diminished depending upon the nature of the stressor.…”

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…Both 5-HT2C antagonists (SB 242084) and inverse agonists (SB 206553) possess anxiolyticlike properties in animal models of anxiety (Kennett et al, 1996(Kennett et al, , 1997. 5-HT2C receptor down-regulation following chronic exercise (Broocks et al, 1999), and desensitization in response to SSRI-treatment (Questad et al, 1997), have been proposed as the mechanisms by which these two treatments are anxiolytic.…”

Dissociable Hormonal, Cognitive and Mood Responses to Neuroendocrine Challenge Evidence for Receptor-Specific Serotonergic Dysregulation in Depressed Mood

“…Broocks et al (Broocks et al 1999) compared neuroendocrine challenge in marathon runners and controls and showed that a blunted cortisol response to m-CPP 0.4 mg/kg, but not to ipsapirone 0.3 mg/kg, differentiated the marathon runners from controls. Broocks et al (2000) also reported a study of neuroendocrine challenge with m-CPP and ipsapirone in groups of patients with panic disorder and/ or agoraphobia and controls.…”