Journal Article

The role of 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors in the signal attenuation rat model of obsessive–compulsive disorder

Shlomit Flaisher-Grinberg, Oded Klavir and Daphna Joel

in International Journal of Neuropsychopharmacology

Published on behalf of International College of Neuropsychopharmacology

Volume 11, issue 6, pages 811-825
Published in print September 2008 | ISSN: 1461-1457
Published online September 2008 | e-ISSN: 1469-5111 | DOI:
The role of 5-HT2A and 5-HT2C receptors in the signal attenuation rat model of obsessive–compulsive disorder

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Serotonin 5-HT2A and 5-HT2C receptors have been implicated in the pathophysiology of obsessive–compulsive disorder (OCD) and in the mechanism mediating the anti-compulsive effects of serotonin reuptake inhibitors. Yet it is currently unclear whether activation or blockade of these receptors would have an anti-compulsive effect. The present study tested the effects of 5-HT2A and 5-HT2C activation and blockade in the signal attenuation rat model of OCD. In this model, ‘compulsive’ behaviour is induced by attenuating a signal indicating that a lever-press response was effective in producing food. Experiments 1–4 revealed that systemic administration of the 5-HT2C antagonist RS 102221 (2 mg/kg) selectively decreases compulsive lever-pressing, whereas systemic administration of the 5-HT2A antagonist MDL 11,939 (0.2–5 mg/kg) or of the 5-HT2A/2C agonist DOI (0.05–5 mg/kg) did not have a selective effect on this behaviour. Experiments 5 and 6 found that systemic co-administration of DOI (0.5 mg/kg) with MDL 11,939 (1 mg/kg) or with RS 102221 (2 mg/kg) had a non-selective effect on lever-press responding, with the former manipulation increasing and the latter manipulation decreasing lever-pressing. Finally, experiment 7 demonstrated that administration of RS 102221 directly into the orbitofrontal cortex also exerts an anti-compulsive effect. The results of these experiments suggest that blockade of 5-HT2C receptors may have an anti-compulsive effect in OCD patients, and that this effect may be mediated by 5-HT2C receptors within the orbitofrontal cortex.

Keywords: Extinction; obsessive–compulsive disorder (OCD); post-training signal attenuation; rat

Journal Article.  8347 words.  Illustrated.

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