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https://hdl.handle.net/1822/62016
Título: | Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion |
Autor(es): | Reyes, B. A. S. Carvalho, A. F. Szot, P. Kalamarides, D. J. Wang, Q. Kirby, L. G. Van Bockstaele, E. J. |
Palavras-chave: | Animals Benzoxazines Brain Cannabinoids Locus Coeruleus Male Mice, Knockout Morpholines Naphthalenes Neurons Norepinephrine Prefrontal Cortex Receptors, Cannabinoid Synapses Cannabinoid receptor type 1 α2-adrenoceptors Medial prefrontal cortex Tyrosine hydroxylase Cannabinoid receptor knock out mice |
Data: | 2017 |
Editora: | Elsevier 1 |
Revista: | Experimental Neurology |
Citação: | Reyes, B. A. S., Carvalho, A. F., Szot, P., Kalamarides, D. J., et al. (2017). Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion. Experimental neurology, 292, 179-192. |
Resumo(s): | 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. |
Tipo: | Artigo |
Descrição: | Accepted Manuscript |
URI: | https://hdl.handle.net/1822/62016 |
DOI: | 10.1016/j.expneurol.2017.03.010 |
ISSN: | 0014-4886 |
e-ISSN: | 1090-2430 |
Versão da editora: | https://www.sciencedirect.com/science/article/pii/S0014488617300705 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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reyes2017.pdf Acesso restrito! | 2,56 MB | Adobe PDF | Ver/Abrir |