The role of 5-HT2A and 5-HT2C receptors in the signal attenuation rat model of obsessive-compulsive disorder.
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. Experiments1-4 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 MDL11,939(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) withMDL11,939 (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-HT2Creceptors may have an anti-compulsive effect in OCD patients, and that this effect may be mediated by5-HT2C receptors within the orbitofrontal cortex.
Flaisher-Grinberg
Shlomit
S
Department of Psychology, Tel Aviv University, Ramat-Aviv, Tel Aviv, Israel.
Klavir
Oded
O
Joel
Daphna
D
D000662:Amphetamines / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003192:Compulsive Behavior / Q000188:drug therapy / Q000209:etiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D010880:Piperidines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D058830:Serotonin 5-HT2 Receptor Antagonists; D013141:Spiro Compounds / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage
C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D000662:Amphetamines; D004338:Drug Combinations; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; D013141:Spiro Compounds; D013449:Sulfonamides; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine