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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. 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.

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The lack of efficient animal models for bipolar disorder (BPD), especially for the manic pole, is a major factor hindering the research of its pathophysiology and the development of improved drug treatments. The present study was designed to identify an appropriate mouse strain for modeling some behavioral domains of mania and to evaluate the effects of drugs using this strain. The study compared the behavior of four strains: Black Swiss, C57Bl/6, CBA/J and A/J mice in a battery of tests that included spontaneous activity; sweet solution preference; light/dark box; resident-intruder; forced-swim and amphetamine-induced hyperactivity. Based on the ‘manic-like’ behavior demonstrated by the Black Swiss strain, the study evaluated the effects of the mood stabilizers valproate and lithium and of the antidepressant imipramine in the same tests using this strain. Results indicated that lithium and valproate attenuate the ‘manic-like’ behavior of Black Swiss mice whereas imipramine had no effects. These findings suggest that Black Swiss mice might be a good choice for modeling several domains of mania and distinguishing the effects of drugs on these specific domains. However, the relevance of the behavioral phenotype of Black Swiss mice to the biology of BPD is unknown at this time and future studies will investigate molecular differences between Black Swiss mice and other strains and asess the interaction between strain and mood stabilizing treatment.