Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder

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Authors: Bruno Aouizerate, Dominique Guehl, Emmanuel Cuny, Alain Rougier, Pierre Burbaud, Jean Tignol, Bernard Bioulac

Published Date February 2005 Volume 2005:1(3) Pages 231 - 243

DOI: http://dx.doi.org/10.2147/NDT.S

Bruno Aouizerate^1,2, Dominique Guehl², Emmanuel Cuny³, Alain Rougier³, Pierre Burbaud², Jean Tignol¹, Bernard Bioulac²

¹Service Universitaire de Psychiatrie, Université Victor Segalen Bordeaux 2, Bordeaux, France; ²Laboratoire de Neurophysiologie, CNRS UMR 5543, Université Victor Segalen Bordeaux 2, Bordeaux, France; ³Service de Neurochirurgie, Université Victor Segalen Bordeaux 2, Bordeaux, France

Abstract: The pathophysiology of obsessive-compulsive disorder (OCD) remains unknown. However, increasing attention has been paid to the putative role of the serotoninergic system, the strongest evidence being based on the widely demonstrated efficacy of serotonin (5HT) reuptake inhibitor antidepressants in the treatment of OCD. The therapeutic effects are correlated with changes in peripheral parameters of 5HT function, which have been found to be altered in OCD, suggesting the possibility of reduced 5HT reuptake capacity. This could reflect a compensatory mechanism presumably due to decreased availability of extracellular 5HT, as evidenced by data derived from direct assessment of central 5HT neurotransmission. The development of new neurochemical probes that explore the sensitivity of various 5HT receptor subtypes has provided precious information. m-Chlorophenylpyperazine (m-CPP), an agonist to 5HT1A, 5HT1D, and 5HT2C receptors, and which also blocks 5HT3 receptors, exacerbates OC symptoms. In contrast, neither MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a 5HT1A and 5HT2C receptor agonist, nor ipsapirone or buspirone, which acts as an agonist to 5HT1A receptors, have any effect on OC symptom severity. This suggests the potential implication of the 5HT1D receptor, as shown by the aggravation of OC manifestations in response to sumatriptan, a selective 5HT1D receptor agonist. The 5HT3 plays no specific role, given the lack of influence of the 5HT3 antagonist ondansetron, on OC symptom intensity. Further studies are required to elucidate the pharmacological molecular determinants of the putative 5HT1D receptor dysfunction.

Keywords: serotonin, serotonin reuptake inhibitors, receptors, serotonin, 5HT1D receptor agonists, obsessive-compulsive disorder