Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats

The heme oxygenase-carbon monoxide pathway has been shown to play an important role in many physiological processes and is capable of altering nociception modulation in the nervous system by stimulating soluble guanylate cyclase (sGC). In the central nervous system, the locus coeruleus (LC) is known...

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Main Authors: P.G. Carvalho-Costa, L.G.S. Branco, C.R.A. Leite-Panissi
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 2016-04-01
Series:Brazilian Journal of Medical and Biological Research
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2016000500601&tlng=en
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author P.G. Carvalho-Costa
L.G.S. Branco
C.R.A. Leite-Panissi
author_facet P.G. Carvalho-Costa
L.G.S. Branco
C.R.A. Leite-Panissi
author_sort P.G. Carvalho-Costa
collection DOAJ
description The heme oxygenase-carbon monoxide pathway has been shown to play an important role in many physiological processes and is capable of altering nociception modulation in the nervous system by stimulating soluble guanylate cyclase (sGC). In the central nervous system, the locus coeruleus (LC) is known to be a region that expresses the heme oxygenase enzyme (HO), which catalyzes the metabolism of heme to carbon monoxide (CO). Additionally, several lines of evidence have suggested that the LC can be involved in the modulation of emotional states such as fear and anxiety. The purpose of this investigation was to evaluate the activation of the heme oxygenase-carbon monoxide pathway in the LC in the modulation of anxiety by using the elevated plus maze test (EPM) and light-dark box test (LDB) in rats. Experiments were performed on adult male Wistar rats weighing 250-300 g (n=182). The results showed that the intra-LC microinjection of heme-lysinate (600 nmol), a substrate for the enzyme HO, increased the number of entries into the open arms and the percentage of time spent in open arms in the elevated plus maze test, indicating a decrease in anxiety. Additionally, in the LDB test, intra-LC administration of heme-lysinate promoted an increase on time spent in the light compartment of the box. The intracerebroventricular microinjection of guanylate cyclase, an sGC inhibitor followed by the intra-LC microinjection of the heme-lysinate blocked the anxiolytic-like reaction on the EPM test and LDB test. It can therefore be concluded that CO in the LC produced by the HO pathway and acting via cGMP plays an anxiolytic-like role in the LC of rats.
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spelling doaj.art-a797a44454fa44b7bb33335b099b5bc92022-12-21T19:23:41ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2016-04-0149510.1590/1414-431x20165135Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in ratsP.G. Carvalho-CostaL.G.S. BrancoC.R.A. Leite-PanissiThe heme oxygenase-carbon monoxide pathway has been shown to play an important role in many physiological processes and is capable of altering nociception modulation in the nervous system by stimulating soluble guanylate cyclase (sGC). In the central nervous system, the locus coeruleus (LC) is known to be a region that expresses the heme oxygenase enzyme (HO), which catalyzes the metabolism of heme to carbon monoxide (CO). Additionally, several lines of evidence have suggested that the LC can be involved in the modulation of emotional states such as fear and anxiety. The purpose of this investigation was to evaluate the activation of the heme oxygenase-carbon monoxide pathway in the LC in the modulation of anxiety by using the elevated plus maze test (EPM) and light-dark box test (LDB) in rats. Experiments were performed on adult male Wistar rats weighing 250-300 g (n=182). The results showed that the intra-LC microinjection of heme-lysinate (600 nmol), a substrate for the enzyme HO, increased the number of entries into the open arms and the percentage of time spent in open arms in the elevated plus maze test, indicating a decrease in anxiety. Additionally, in the LDB test, intra-LC administration of heme-lysinate promoted an increase on time spent in the light compartment of the box. The intracerebroventricular microinjection of guanylate cyclase, an sGC inhibitor followed by the intra-LC microinjection of the heme-lysinate blocked the anxiolytic-like reaction on the EPM test and LDB test. It can therefore be concluded that CO in the LC produced by the HO pathway and acting via cGMP plays an anxiolytic-like role in the LC of rats.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2016000500601&tlng=enHeme oxygenaseCarbon monoxideLocus coeruleusAnxietyElevated plus maze, Light/dark box
spellingShingle P.G. Carvalho-Costa
L.G.S. Branco
C.R.A. Leite-Panissi
Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats
Brazilian Journal of Medical and Biological Research
Heme oxygenase
Carbon monoxide
Locus coeruleus
Anxiety
Elevated plus maze, Light/dark box
title Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats
title_full Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats
title_fullStr Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats
title_full_unstemmed Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats
title_short Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats
title_sort activation of locus coeruleus heme oxygenase carbon monoxide pathway promoted an anxiolytic like effect in rats
topic Heme oxygenase
Carbon monoxide
Locus coeruleus
Anxiety
Elevated plus maze, Light/dark box
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2016000500601&tlng=en
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AT lgsbranco activationoflocuscoeruleushemeoxygenasecarbonmonoxidepathwaypromotedananxiolyticlikeeffectinrats
AT craleitepanissi activationoflocuscoeruleushemeoxygenasecarbonmonoxidepathwaypromotedananxiolyticlikeeffectinrats