کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5629160 1580147 2017 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research PaperCortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion
ترجمه فارسی عنوان
تحقیق، مقاله، تحلیل، عملکرد و انطباق آدرنرژیکتیکورتور شرکت کننده در شرایط حذف گیرنده کانابینوئید
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
چکیده انگلیسی


- CB1r KO mice showed an α2-adrenoceptor-mediated decrease in mPFC cell excitability.
- α2- and β1-adrenoceptor levels decreased in mPFC while TH increased in LC in CB1r KO mice.
- CB1r and α2-adrenoceptors are co-localized post-synaptically in the same mPFC neurons.
- α2A-adrenoceptor binding is unchanged in mPFC following acute or chronic WIN 55,212-2 but increased following withdrawal.
- These data provide convergent lines of evidence indicating cannabinoid regulation of the cortical adrenergic system.

A neurochemical target at which cannabinoids interact to have global effects on behavior is brain noradrenergic circuitry. Acute and repeated administration of a cannabinoid receptor synthetic agonist is capable of increasing multiple indices of noradrenergic activity. This includes cannabinoid-induced 1) increases in norepinephrine (NE) release in the medial prefrontal cortex (mPFC); 2) desensitization of cortical α2-adrenoceptor-mediated effects; 3) activation of c-Fos in brainstem locus coeruleus (LC) noradrenergic neurons; and 4) increases in anxiety-like behaviors. In the present study, we sought to examine adaptations in adrenoceptor expression and function under conditions of cannabinoid receptor type 1 (CB1r) deletion using knockout (KO) mice and compare these to wild type (WT) controls. Electrophysiological analysis of α2-adrenoceptor-mediated responses in mPFC slices in WT mice showed a clonidine-induced α2-adrenoceptor-mediated increase in mPFC cell excitability coupled with an increase in input resistance. In contrast, CB1r KO mice showed an α2-adrenoceptor-mediated decrease in mPFC cell excitability. We then examined protein expression levels of α2- and β1-adrenoceptor subtypes in the mPFC as well as TH expression in the locus coeruleus (LC) of mice deficient in CB1r. Both α2- and β1-adrenoceptors exhibited a significant decrease in expression levels in CB1r KO mice when compared to WT in the mPFC, while a significant increase in TH was observed in the LC. To better define whether the same cortical neurons express α2A-adrenoceptor and CB1r in mPFC, we utilized high-resolution immunoelectron microscopy. We localized α2A-adrenoceptors in a knock-in mouse that expressed a hemoagglutinin (HA) tag downstream of the α2A-adrenoceptor promoter. Although the α2A-adrenoceptor was often identified pre-synaptically, we observed co-localization of CB1r with α2-adrenoceptors post-synaptically in the same mPFC neurons. Finally, using receptor binding, we confirmed prior results showing that α2A-adrenoceptor is unchanged in mPFC following acute or chronic exposure to the synthetic cannabinoid receptor agonist, WIN 55,212-2, but is increased, following chronic treatment followed by a period of abstinence. Taken together, these data provide convergent lines of evidence indicating cannabinoid regulation of the cortical adrenergic system.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 292, June 2017, Pages 179-192
نویسندگان
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