Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat

The pharmacological profile of cannabigerol (CBG), which acid form constitutes the main precursor of the most abundant cannabinoids, has been scarcely studied. It has been reported to target α2-adrenoceptor and 5-HT1A receptor. The locus coeruleus (LC) and the dorsal raphe nucleus (DRN) are the main...

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Autores: Mendiguren Ordorica, Aitziber, Aostri Parga, Erik, Rodilla Ojeda, Irati, Pujana, Iker, Noskova, Ekaterina, Pineda Ortiz, Joseba Gotzon
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/61896
Acceso en línea:http://hdl.handle.net/10810/61896
Access Level:acceso abierto
Palabra clave:dorsal raphe nucleus
slice
firing
noradrenaline
locus coeruleus
cannabigerol
anxiety, serotonin
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spelling Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in ratMendiguren Ordorica, AitziberAostri Parga, ErikRodilla Ojeda, IratiPujana, IkerNoskova, EkaterinaPineda Ortiz, Joseba Gotzondorsal raphe nucleusslicefiringnoradrenalinelocus coeruleuscannabigerolanxiety, serotoninThe pharmacological profile of cannabigerol (CBG), which acid form constitutes the main precursor of the most abundant cannabinoids, has been scarcely studied. It has been reported to target α2-adrenoceptor and 5-HT1A receptor. The locus coeruleus (LC) and the dorsal raphe nucleus (DRN) are the main serotonergic (5-HT) and noradrenergic (NA) areas in the rat brain, respectively. We aimed to study the effect of CBG on the firing rate of LC NA cells and DRN 5-HT cells and on α2-adrenergic and 5-HT1A autoreceptors by electrophysiological techniques in male Sprague-Dawley rat brain slices. The effect of CBG on the novelty-suppressed feeding test (NSFT) and the elevated plus maze test (EPMT) and the involvement of the 5-HT1A receptor was also studied. CBG (30 μM, 10 min) slightly changed the firing rate of NA cells but failed to alter the inhibitory effect of NA (1–100 µM). However, in the presence of CBG the inhibitory effect of the selective α2-adrenoceptor agonist UK14304 (10 nM) was decreased. Perfusion with CBG (30 μM, 10 min) did not change the firing rate of DRN 5-HT cells or the inhibitory effect of 5-HT (100 μM, 1 min) but it reduced the inhibitory effect of ipsapirone (100 nM). CBG failed to reverse ipsapirone-induced inhibition whereas perfusion with the 5-HT1A receptor antagonist WAY100635 (30 nM) completely restored the firing rate of DRN 5-HT cells. In the EPMT, CBG (10 mg/kg, i.p.) significantly increased the percentage of time the rats spent on the open arms and the number of head-dipping but it reduced the anxiety index. In the NSFT, CBG decreased the time latency to eat in the novel environment but it did not alter home-cage consumption. The effect of CBG on the reduction of latency to feed was prevented by pretreatment with WAY100635 (1 mg/kg, i.p.). In conclusion, CBG hinders the inhibitory effect produced by selective α2-adrenoceptor and 5-HT1A receptor agonists on the firing rate of NA-LC and 5-HT-DRN neurons by a yet unknown indirect mechanism in rat brain slices and produces anxiolytic-like effects through 5-HT1A receptor.This work was supported by the Ministerio de Sanidad, Consumo y Bienestar Social. Delegación del Gobierno para el Plan Nacional Sobre Drogas, PND 2018I025, (PND18/04) and University of the Basque Country (UPV/EHU) (Grant GIU19/076). EA and IR were supported by a predoctoral fellowship from the Basque and Spanish Government, respectively.Frontiers Media202320232023info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/61896reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.frontiersin.org/articles/10.3389/fphar.2023.1183019/fullinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/© 2023 Mendiguren, Aostri, Rodilla, Pujana, Noskova and Pineda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Atribución 3.0 Españaoai:addi.ehu.eus:10810/618962026-06-18T09:23:17Z
dc.title.none.fl_str_mv Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat
title Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat
spellingShingle Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat
Mendiguren Ordorica, Aitziber
dorsal raphe nucleus
slice
firing
noradrenaline
locus coeruleus
cannabigerol
anxiety, serotonin
title_short Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat
title_full Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat
title_fullStr Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat
title_full_unstemmed Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat
title_sort Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat
dc.creator.none.fl_str_mv Mendiguren Ordorica, Aitziber
Aostri Parga, Erik
Rodilla Ojeda, Irati
Pujana, Iker
Noskova, Ekaterina
Pineda Ortiz, Joseba Gotzon
author Mendiguren Ordorica, Aitziber
author_facet Mendiguren Ordorica, Aitziber
Aostri Parga, Erik
Rodilla Ojeda, Irati
Pujana, Iker
Noskova, Ekaterina
Pineda Ortiz, Joseba Gotzon
author_role author
author2 Aostri Parga, Erik
Rodilla Ojeda, Irati
Pujana, Iker
Noskova, Ekaterina
Pineda Ortiz, Joseba Gotzon
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv dorsal raphe nucleus
slice
firing
noradrenaline
locus coeruleus
cannabigerol
anxiety, serotonin
topic dorsal raphe nucleus
slice
firing
noradrenaline
locus coeruleus
cannabigerol
anxiety, serotonin
description The pharmacological profile of cannabigerol (CBG), which acid form constitutes the main precursor of the most abundant cannabinoids, has been scarcely studied. It has been reported to target α2-adrenoceptor and 5-HT1A receptor. The locus coeruleus (LC) and the dorsal raphe nucleus (DRN) are the main serotonergic (5-HT) and noradrenergic (NA) areas in the rat brain, respectively. We aimed to study the effect of CBG on the firing rate of LC NA cells and DRN 5-HT cells and on α2-adrenergic and 5-HT1A autoreceptors by electrophysiological techniques in male Sprague-Dawley rat brain slices. The effect of CBG on the novelty-suppressed feeding test (NSFT) and the elevated plus maze test (EPMT) and the involvement of the 5-HT1A receptor was also studied. CBG (30 μM, 10 min) slightly changed the firing rate of NA cells but failed to alter the inhibitory effect of NA (1–100 µM). However, in the presence of CBG the inhibitory effect of the selective α2-adrenoceptor agonist UK14304 (10 nM) was decreased. Perfusion with CBG (30 μM, 10 min) did not change the firing rate of DRN 5-HT cells or the inhibitory effect of 5-HT (100 μM, 1 min) but it reduced the inhibitory effect of ipsapirone (100 nM). CBG failed to reverse ipsapirone-induced inhibition whereas perfusion with the 5-HT1A receptor antagonist WAY100635 (30 nM) completely restored the firing rate of DRN 5-HT cells. In the EPMT, CBG (10 mg/kg, i.p.) significantly increased the percentage of time the rats spent on the open arms and the number of head-dipping but it reduced the anxiety index. In the NSFT, CBG decreased the time latency to eat in the novel environment but it did not alter home-cage consumption. The effect of CBG on the reduction of latency to feed was prevented by pretreatment with WAY100635 (1 mg/kg, i.p.). In conclusion, CBG hinders the inhibitory effect produced by selective α2-adrenoceptor and 5-HT1A receptor agonists on the firing rate of NA-LC and 5-HT-DRN neurons by a yet unknown indirect mechanism in rat brain slices and produces anxiolytic-like effects through 5-HT1A receptor.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/61896
url http://hdl.handle.net/10810/61896
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.frontiersin.org/articles/10.3389/fphar.2023.1183019/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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