Skip to main content Accessibility help
×
Home

Serotonin Dysfunction in Pathological Gamblers: Increased Prolactin Response to Oral m-CPP Versus Placebo

Published online by Cambridge University Press:  07 November 2014

Abstract

Objective

Acute administration of the partial serotonin (5-HT) agonist meta-chlorophenylpi-perazine (m-CPP), that is used also as a street drug, has been reported to induce a “high” and craving response in various impulsive and sub-stance addiction disorders.

Introduction

To clarify altered 5-HT metabolism in pathological gamblers and to explore the specific role of serotonergic system in non substance addictions, we assessed behavioral (“high” and “craving”) and neuroendocrine (prolactin and cortisol) responses to an oral single dose of m-CPP and placebo in pathological gamblers and matched controls. Moreover, the relationship between neuroendocrine outcome and clinical severity has been assessed.

Method

Twenty-six pathological gamblers and 26 healthy control subjects enter a double-blind, placebo-controlled-crossed administration of orally dose m-CPP 0.5 mg/kg. Outcome measures included prolactin and cortisol levels, gambling severity, mood, craving and “high” scales.

Results

Pathological gamblers had significantly increased prolactin response compared to controls at 180 minutes and at 210 minutes post–administration. Greater pathological gamblers severity correlated with increased neuroendocrine responsiveness to m-CCP, suggesting greater 5-HT dysregulation. Pathological gambling patients had a significantly increased “high” sensation after m-CPP administration compared with control.

Conclusion

These results provide additional evidence for 5-HT disturbance in pathological gamblers and they support the hypotheses that the role of the 5-HT dysfunction related to the experience of “high” might represent the path-way that leads to dyscontrolled behavior in patho-logical gamblers. Furthermore, the “high” feeling induced by m-CPP in pathological subjects may represent a marker of vulnerability to both behav-ioral and substance addictions.

Type
Original research
Copyright
Copyright © Cambridge University Press 2006

Access options

Get access to the full version of this content by using one of the access options below.

References

1. Feuchtl, A, Bagli, M, Stephan, R, et al. Pharmacokinetics of m-chlorophenylpiperazine after intravenous and oral administration in healthy male volunteers: implication for the pharmacodynamic profile. Pharmacopsychiatry. 2004:37:180188.CrossRefGoogle ScholarPubMed
2. Moss, HB, Yao, JK, Panzak, GL. Serotonergic responsivity and behavioral dimensions in antisocial personality disorder with substance abuse. Biol Psychiatry. 1990:28:325338.CrossRefGoogle ScholarPubMed
3. Hollander, E, Stein, DJ, DeCaria, CM, et al. Serotonergic sensitivity in borderline personality disorder: preliminary findings. Am J Psychiatry. 1994:151:277280.Google ScholarPubMed
4. Stein, OJ, Hollander, E, Cohen, L, Simeon, D, Aronowitz, B. Serotonergic responsivity in trichotillomania: neuroendrocrine effects of m-chlorophenylpiperazine. Biol Psychiatry. 1995:37:414416.CrossRefGoogle ScholarPubMed
5. Benkelfat, C, Murphy, DL, Hill, JL, George, DT, Nutt, D, Linnoila, M. Ethanol like proper-ties of the serotonergic partial agonist m-chlorophenylpiperazine in chronic alcoholic patients. Arch Gen Psychiatry. 1991:48:383.CrossRefGoogle Scholar
6. Buydens-Branchey, L, Branchey, M, Fergeson, P Hudson, J, McKernin, C. Euphorogenic properties of the serotonergic partial agonist m-chlorophenylpiperazine in cocaine addicts. Arch Gen Psychiatry. 1993:50:10011002.CrossRefGoogle ScholarPubMed
7. Krystal, JH, Webb, E, Cooney, N, Kranzler, HR, Charney, DS. Specificity of ethanol like effects elirefd by serotonergic and noradrenergic mechanisms. Arch Gen Psychiatry. 1994:51:898911.CrossRefGoogle Scholar
8. Meltzer, HY, Maes, M. Pindolol pretreatment blocks stimulation by meta-chloro-phenylpiperazine of prolactin but not cortisol secretion in normal men. Psychiatry Res. 1995:58:8998.CrossRefGoogle Scholar
9. Holden, C. “Behavioral” addictions: do they exist? Science. 2001:294:980982.CrossRefGoogle ScholarPubMed
10. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. text rev. Washington, DC: American Psychiatric Association: 2000.Google Scholar
11. Petry, NM. Should the scope of addictive behaviors be broadened to include pathological gambling? Addiction. 2006:101(suppl 1):152–60.CrossRefGoogle ScholarPubMed
12. Potenza, MN. Should addictive disorders include non-substance-related conditions? Addiction.2006;101(suppl 1):142151.CrossRefGoogle ScholarPubMed
13. Dodd, ML, Klos, KJ, Bower, JH, Geda, YE, Josephs, KA, Ahlskog, JE. Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol. 2005:62:13771381.CrossRefGoogle ScholarPubMed
14. Grant, JE, Potenza, MN, Hollander, E, et al. Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry. 2006:163:303312.CrossRefGoogle ScholarPubMed
15. Nestler, EJ. Is there a common molecular pathway for addiction? Nat Neurosci. 2005:8:14451449.CrossRefGoogle Scholar
16. Potenza, M.N. The neurobiology of pathological gambling. Semin Clin Neuropsychiatry. 2001:6:217–26.CrossRefGoogle ScholarPubMed
17. DeCaria, C, Hollander, E, Nora, R, et al. Gambling: biological/genetic, treatment, government, and gambling concerns: neurobiology of pathological gambling. Paper presented at: Annual Meeting of the American Psychiatric Association. May, 1997: San Diego, Calif.Google Scholar
18. Pallanti, S, DeCaria, CM, Grant, JE, Urpe, M, Hollander, E. Reliability and validity of the Pathological Gambling Adaptation of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS). J Gambl Stud 2005:21:431443.CrossRefGoogle Scholar
19. Vythilingum, B, Hugo, CJ, Maritz, JS, Pienaar, W, Stein, DJ. Pharmacological challenge with a serotonin 1D agonist in alcohol dependence. BMC Psychiatry. 2005:24:5:31.CrossRefGoogle Scholar
20. Charney, DS, Heninger, GR, Breier, A. Noradrenergic function in panic anxiety. Effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1984;41:751763.CrossRefGoogle ScholarPubMed
21. Zohar, J, Mueller, EA, Insel, TR, Zohar-Kadouch, RC, Murphy, DL. Serotonergic responsivity in obsessive-compulsive disorder: comparison of patients and healty controls. Arch Gen Psychiatry. 1987:44:946951.CrossRefGoogle Scholar
22. SPSS for Windows. Chicago, Ill: SPSS, Inc.: 1998 Google Scholar
23. Enoch, MA, Greenberg, BD, Murphy, DL, Goldman, D. Sexually dimorphic relationship of a 5-HT2A promoter polymorphism with obsessive-compulsive disorder. Biol Psychiatry. 2001:49:385388.CrossRefGoogle ScholarPubMed
24. Bossong, MG, Van Dijk, JP, Niesink, RJ. Methylone and m-CPR two new drugs of abuse? Addict Biol. 2005:10:321323.CrossRefGoogle Scholar
25. Tancer, ME, Johanson, CE. The subjective effects of MDMA and m-CPP in moderate MDMA users. Drug Alcohol Depend. 2001:65:97101.CrossRefGoogle ScholarPubMed
26. Hollander, E, DeCaria, CM, Finkell, JN, Begaz, T, Wong, CM, Cartwright, C. A randomized double-blind fluvoxamine/placebo crossover trial in pathologic gambling. Biol Psychiatry. 2000:47:813817.CrossRefGoogle ScholarPubMed
27. Hollander, E, DeCaria, CM, Nitescu, A, et al. Serotonergic function in obsessive-compulsive disorder: Behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healty volunteers. Arch Gen Psychiatry. 1992:49:2128.CrossRefGoogle Scholar
28. Pallanti, S, Bernardi, A, Allen, W, et al. Noradrenergic deficit in pathological gambling: blunted growth hormone response to oral clonidine vs. placebo. Biol Psychiatry. In press.Google Scholar
29. Buydens-Branchey, L, Branchey, M, Fergeson, P, Hudson, J, McKernin, C. Craving for cocaine in addicted user. Role of serotonergic mechanism. Am J Addict. 1997:6:6573.Google Scholar
30. Buydens-Branchey, L, Branchey, M, Fergeson, P, Hudson, J, McKernin, C. The meta-chlorophenylpiperazine challenge test in cocaine addicts: hormonal and psychological responses. Biol Psychiatry. 1997:41:10711086.CrossRefGoogle ScholarPubMed
31. Van de Kar, LD, Karteszi, M, Bethea, CL, Ganong, WF. Serotonergic stimulation of prolactin and corticosterone secretion is mediated by different pathways from the mediobasal hypothalamus. Neuroendocrinology. 1985:41:380384.CrossRefGoogle ScholarPubMed
32. Bagdy, G, Calogero, AE, Murphy, DL, Szemeredi, K. Serotonin agonists cause parallel activation of the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis in conscious rats. Endocrinology. 1989:125:26642669.CrossRefGoogle ScholarPubMed
33. Gibbs, DM, Vale, W. Effect of the serotonin reuptake inhibitor fluoxetine on corticotro-pin-releasing factor and vasopressin secretion into hypophysial portal blood. Brain Res. 1983:280:176179.CrossRefGoogle ScholarPubMed
34. Fuller, RW, Snoddy, HD. Effect of serotonin-releasing drugs on serum corticosterone concentration in rats. Neuroendocrinology. 1980:31:96100.CrossRefGoogle ScholarPubMed
35. Fuller, RW. Serotonergic stimulation of pituitary-adrenocortical function in rats. Neuroendocrinology. 1981:32:118127.CrossRefGoogle ScholarPubMed
36. Koob, GF, Sanna, PP, Bloom, FE. Neuroscience of Addiction. Neuron. 1998:467476.CrossRefGoogle ScholarPubMed

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 0
Total number of PDF views: 23 *
View data table for this chart

* Views captured on Cambridge Core between September 2016 - 20th January 2021. This data will be updated every 24 hours.

Hostname: page-component-76cb886bbf-pdn9z Total loading time: 0.374 Render date: 2021-01-20T19:02:29.705Z Query parameters: { "hasAccess": "0", "openAccess": "0", "isLogged": "0", "lang": "en" } Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false }

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Serotonin Dysfunction in Pathological Gamblers: Increased Prolactin Response to Oral m-CPP Versus Placebo
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Serotonin Dysfunction in Pathological Gamblers: Increased Prolactin Response to Oral m-CPP Versus Placebo
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Serotonin Dysfunction in Pathological Gamblers: Increased Prolactin Response to Oral m-CPP Versus Placebo
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *