A comparison of the behavioral effects of oral versus intravenous mCPP administration in OCD patients and the effect of metergoline prior to IV mCPP

Pigott, Teresa A.; Hill, James L.; Grady, Tana A.; L'Heureux, Francine; Bernstein, Suzanne E.; Rubenstein, Cheryl S.; Murphy, Dennis L.

doi:10.1016/0006-3223(93)90272-f

Cited by 95 publications

(34 citation statements)

References 31 publications

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“…In contrast, ipsapirone induced a significant increase of cortisol of the same magnitude in both the marathon and the control group. Because other studies using various 5-HT antagonists have consistently shown that the effects of m-CPP on prolactin, CRH, ACTH, and cortisol are predominantly mediated by 5-HT 2C receptors (Aulakh et al 1992;Calogero et al 1993;Mazzola-Pomietto et al 1995;Murphy et al 1991;Pigott et al 1993;Seibyl et al 1991), our results are in agreement with the hypothesis that regular endurance training leads to a downregulation of central 5-HT 2C receptors. This conclusion is supported by the attenuated prolactin response in the marathon group, which is also mediated mainly by postsynaptic 5-HT 2C receptors (Aulakh et al 1992;Murphy et al 1991).…”

Section: Discussionsupporting

confidence: 92%

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

Broocks

Meyer²,

George

et al. 1999

Neuropsychopharmacology

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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...

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Section: Discussionsupporting

confidence: 92%

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

Broocks

Meyer²,

George

et al. 1999

Neuropsychopharmacology

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“…Although the m-CPP dose was 20% lower in comparison to our former Ž . dose Pigott et al, 1993 , the psychobehavioral response was very similar.…”

Section: Discussionmentioning

confidence: 49%

“…1992a and intravenous administration of m-CPP Ž . Pigott et al, 1993 . In contrast, two studies of OCD patients using oral andror intravenous in-Ž fusions of m-CPP 0.5 mgrkg and 0.1 mgrkg, . respectively did not report any increase of OCD Ž symptoms Charney et al, 1988;Goodman et al, .…”

Section: Discussionmentioning

confidence: 99%

“…M-CPP was administered in a 20-min infusion in the latter two studies, whereas it was delivered in a 90-s bolus in the current study and in the other Ž . positive intravenous study Pigott et al, 1993 . Also, the small sample size, interrater variability, differences in the assessment procedures or the characteristics of the patient samples could have been involved.…”

Section: Discussionmentioning

confidence: 99%

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Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive–compulsive disorder (OCD): behavioral and biological results

Broocks

Pigott

Hill

et al. 1998

Psychiatry Research

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Ž. Ž . Obsessive᎐compulsive disorder OCD has been linked to abnormal function of brain serotonin 5-HT pathways. Since ondansetron is a highly selective 5-HT receptor antagonist, the present study was undertaken to investigate 3 Ž . 5-HT function in OCD. We administered m-CPP 0.08 mgrkg i.v. and the potent 5-HT antagonist, ondansetron 3 3 Ž . Ž 0.15 mgrkg i.v. , to 11 OCD patients. All of the subjects received four separate challenges m-CPP q placebo, . m-CPP q ondansetron, ondansetron q placebo and placebo q placebo . In comparison to placebo, administration of m-CPP was associated with significant behavioral effects, particularly self-rated measures of anxiety, altered self-reality, functional deficit and OCD symptoms. Pretreatment with ondansetron did not affect any of the self-rated behavioral symptoms. After administration of m-CPP relative to placebo, significant increases in plasma cortisol and prolactin were found. These changes were not affected by ondansetron. In conclusion, our results do not support the hypotheses that 5-HT receptor-mediated mechanisms modulate m-CPP's behavioral and neuroendocrine effects in 3 patients with OCD. ᮊ

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“…13 In addition, the ability of metergoline to antagonize the behavioural effects of intravenous mCPP suggests that these responses are mediated by 5-HT1/5-HT2 receptors. 14 The −1438G/A promoter polymorphism of the 5-HT 2A gene seems to be implicated in other neuropsychiatric disorders such as schizophrenia, 15 seasonal affective disorder 16 and alcohol dependence. 17 Especially, AN restricting type has been found to be associated with the A-allele of the −1438G/A promoter polymorphism.…”

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confidence: 99%

5-HT2A promoter polymorphism −1438G/A in children and adolescents with obsessive-compulsive disorders

et al. 2002

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Keywords: obsessive-compulsive disorder; 5HT 2A polymorphism; association study; child and adolescent psychiatry Positive association between obsessive compulsive disorder (OCD) and the A-allele of the 5-HT 2A -receptor promoter polymorphism −1438G/A has recently been reported in adults. We performed an association analysis of this polymorphism in 55 children and adolescents with OCD and in 223 controls consisting of unrelated students. We detected statistically significant differences in genotype (P < 0.05) and allele frequencies (P < 0.05) between individuals with OCD and controls. In this, to our knowledge, first association study based on children and adolescents with OCD, we confirm an association of the A-allele of the 5-HT2A receptor gene with OCD.

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A comparison of the behavioral effects of oral versus intravenous mCPP administration in OCD patients and the effect of metergoline prior to IV mCPP

Cited by 95 publications

References 31 publications

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

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

Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive–compulsive disorder (OCD): behavioral and biological results

5-HT2A promoter polymorphism −1438G/A in children and adolescents with obsessive-compulsive disorders

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