Abstract
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.
Original language | English |
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Pages (from-to) | 811-825 |
Number of pages | 15 |
Journal | International Journal of Neuropsychopharmacology |
Volume | 11 |
Issue number | 6 |
DOIs | |
State | Published - Sep 2008 |
Externally published | Yes |
Keywords
- Extinction
- Obsessive-compulsive disorder (OCD)
- Post-training signal attenuation
- Rat
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health
- Pharmacology (medical)