کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2495057 1115593 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: Evidence for altered striatal function
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: Evidence for altered striatal function
چکیده انگلیسی

PDE10A is a newly identified phosphodiesterase that is highly expressed by the medium spiny projection neurons of the striatum. In order to investigate the physiological role of PDE10A in the central nervous system, PDE10A knockout mice (PDE10A−/−) were characterized both behaviorally and neurochemically. PDE10A−/− mice showed decreased exploratory activity and a significant delay in the acquisition of conditioned avoidance behavior when compared to wild-type (PDE10A+/+) mice. However, in a variety of other well-characterized behavioral tasks, including the elevated plus maze (anxiety), forced swim test (depression), hot plate (nociception) and two memory models (passive avoidance and Morris water maze), PDE10A−/− mice performed similarly to wild-type mice. When challenged with PCP or MK-801, PDE10A−/− mice showed a blunted locomotor response in comparison to PDE10A+/+ mice. In contrast, PDE10A−/− and PDE10A+/+ mice responded similarly to the locomotor stimulating effects of amphetamine and methamphetamine. Our findings suggest that PDE10A is involved in regulating striatal output, possibly by reducing the sensitivity of medium spiny neurons to glutamatergic excitation. These results are discussed in relationship to the hypothesis that PDE10A inhibition presents a novel treatment for psychosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 51, Issue 2, August 2006, Pages 374–385
نویسندگان
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