کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5814742 1556643 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Selective brain region activation by histamine H3 receptor antagonist/inverse agonist ABT-239 enhances acetylcholine and histamine release and increases c-Fos expression
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Selective brain region activation by histamine H3 receptor antagonist/inverse agonist ABT-239 enhances acetylcholine and histamine release and increases c-Fos expression
چکیده انگلیسی

Histamine axons originate solely from the tuberomamillary nucleus (TMN) to innervate almost all brain regions. This feature is consistent with a function for histamine over a host of physiological processes, including regulation of appetite, body temperature, cognitive processes, pain perception and sleep-wake cycle. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulations. Here we report that systemic administration of the non-imidazole histamine H3 receptor antagonist 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile (ABT-239, 3 mg/kg) increased c-Fos expression dose-dependently in rat cortex and nucleus basalis magnocellularis (NBM) but not in the nucleus accumbens (NAcc) nor striatum, and augmented acetylcholine and histamine release from rat prefrontal cortex. To further understand functional histaminergic pathways in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the TMN. Perfusion of the TMN with ABT-239 (10 μM) increased histamine release from the TMN, NBM, and cortex, but not from the striatum or NAcc. When administered locally, ABT-239 increased histamine release from the NBM, but not from the NAcc. Systemic as well as intra-TMN administration of ABT-239 increased c-Fos expression in the NBM, and cortex, but not in the striatum or NAcc. Thus, as defined by their sensitivity to ABT-239, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. This implies independent functions of subsets of histamine neurons according to their terminal projections, with relevant consequences for the development of specific compounds that affect only subsets of histamine neurones, thus increasing target specificity.

► ABT-239 (i.p.) increased c-Fos expression in rat cortex and NBM but not NAcc or striatum. ► ABT-239 (i.p.) increased cortical histamine and ACh release. ► TMN perfusion with ABT-239 released histamine selectively in the NBM and cortex. ► TMN perfusion with ABT-239 activated c-Fos selectively in the NBM and cortex.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 70, July 2013, Pages 131-140
نویسندگان
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