کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6227997 1276492 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Essential Role for Orbitofrontal Serotonin 1B Receptors in Obsessive-Compulsive Disorder-Like Behavior and Serotonin Reuptake Inhibitor Response in Mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Essential Role for Orbitofrontal Serotonin 1B Receptors in Obsessive-Compulsive Disorder-Like Behavior and Serotonin Reuptake Inhibitor Response in Mice
چکیده انگلیسی

BackgroundPerseveration and sensorimotor gating deficits are core features of obsessive-compulsive disorder (OCD). Serotonin 1B receptor (5-HT1BR) agonists exacerbate OCD symptoms in patients and induce perseveration and sensorimotor gating deficits in mice. Serotonin reuptake inhibitors (SRIs), but not noradrenaline reuptake inhibitors (NRIs), reduce OCD symptoms following 4 to 8 weeks of treatment. Using mice, we compared the effects of chronic SRI versus NRI treatment on 5-HT1BR-induced OCD-like behavior and 5-HT1BR sensitivity in orbitofrontal-subcortical OCD circuits. Furthermore, we localized the 5-HT1BR population that mediates OCD-like behavior.MethodsMice chronically received the SRI clomipramine or the NRI desipramine and were examined for 5-HT1BR-induced OCD-like behavior or 5-HT1BR binding and G-protein coupling in caudate putamen, nucleus accumbens, and orbitofrontal cortex. Separate mice were tested for OCD- or depression-like behavior following 4, 14, 21, 28, or 56 days of SRI treatment. Finally, OCD-like behavior was assessed following intra-orbitofrontal 5-HT1BR agonist infusion or intra-orbitofrontal 5-HT1BR antagonist infusion coupled with systemic 5-HT1BR agonist treatment.ResultsEffective, but not ineffective, OCD treatments reduced OCD-like behavior in mice with a time course that parallels the delayed therapeutic onset in OCD patients and downregulated 5-HT1BR expression in the orbitofrontal cortex. Intra-orbitofrontal 5-HT1BR agonist infusion induced OCD-like behavior, and intra-orbitofrontal 5-HT1BR antagonist infusion blocked OCD-like effects of systemic 5-HT1BR agonist treatment.ConclusionsThese results indicate that orbitofrontal 5-HT1BRs are necessary and sufficient to induce OCD-like behavior in mice and that SRI pharmacotherapy reduces OCD-like behavior by desensitizing orbitofrontal 5-HT1BRs. Our findings suggest an essential role for orbitofrontal 5-HT1BRs in OCD pathophysiology and treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 70, Issue 11, 1 December 2011, Pages 1039-1048
نویسندگان
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