Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-23T21:18:26.187Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  07 November 2014

Stefano Pallanti ,
Silvia Bernardi ,
Leonardo Quercioli ,
Concetta DeCaria  and
Eric Hollander
Get access Rights & Permissions [Opens in a new window]

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
Information
CNS Spectrums , Volume 11 , Issue 12 , December 2006 , pp. 956 - 965
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. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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. 2004:37:180–188.Google Scholar
2. Moss, HB, Yao, JK, Panzak, GL. Serotonergic responsivity and behavioral dimensions in antisocial personality disorder with substance abuse. Biol Psychiatry. 1990:28:325–338.Google Scholar
3. Hollander, E, Stein, DJ, DeCaria, CM, et al. Serotonergic sensitivity in borderline personality disorder: preliminary findings. Am J Psychiatry. 1994:151:277–280.Google Scholar
4. Stein, OJ, Hollander, E, Cohen, L, Simeon, D, Aronowitz, B. Serotonergic responsivity in trichotillomania: neuroendrocrine effects of m-chlorophenylpiperazine. Biol Psychiatry. 1995:37:414–416.Google Scholar
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.Google 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. 1993:50:1001–1002.Google Scholar
7. Krystal, JH, Webb, E, Cooney, N, Kranzler, HR, Charney, DS. Specificity of ethanol like effects elicited by serotonergic and noradrenergic mechanisms. Arch Gen Psychiatry. 1994:51:898–911.Google 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. 1995:58:89–98.Google Scholar
9. Holden, C. “Behavioral” addictions: do they exist? Science. 2001:294:980–982.Google Scholar
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.Google Scholar
12. Potenza, MN. Should addictive disorders include non-substance-related conditions? Addiction.2006;101(suppl 1):142–151.Google Scholar
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. 2005:62:1377–1381.Google Scholar
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. 2006:163:303–312.Google Scholar
15. Nestler, EJ. Is there a common molecular pathway for addiction? Nat Neurosci. 2005:8:1445–1449.Google Scholar
16. Potenza, M.N. The neurobiology of pathological gambling. Semin Clin Neuropsychiatry. 2001:6:217–26.Google Scholar
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 2005:21:431–443.Google 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.Google 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;41:751–763.Google Scholar
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. 1987:44:946–951.Google 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. 2001:49:385–388.Google Scholar
24. Bossong, MG, Van Dijk, JP, Niesink, RJ. Methylone and m-CPR two new drugs of abuse? Addict Biol. 2005:10:321–323.Google Scholar
25. Tancer, ME, Johanson, CE. The subjective effects of MDMA and m-CPP in moderate MDMA users. Drug Alcohol Depend. 2001:65:97–101.Google Scholar
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. 2000:47:813–817.Google Scholar
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. 1992:49:21–28.Google 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. 1997:6:65–73.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. 1997:41:1071–1086.Google Scholar
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. 1985:41:380–384.Google Scholar
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. 1989:125:2664–2669.Google Scholar
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. 1983:280:176–179.Google Scholar
34. Fuller, RW, Snoddy, HD. Effect of serotonin-releasing drugs on serum corticosterone concentration in rats. Neuroendocrinology. 1980:31:96–100.Google Scholar
35. Fuller, RW. Serotonergic stimulation of pituitary-adrenocortical function in rats. Neuroendocrinology. 1981:32:118–127.Google Scholar
36. Koob, GF, Sanna, PP, Bloom, FE. Neuroscience of Addiction. Neuron. 1998:467–476.Google Scholar