Cargando…

Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress

Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the baso...

Descripción completa

Detalles Bibliográficos
Autores principales: Guerrero-Bautista, Rocío, Franco-García, Aurelio, Hidalgo, Juana M., Fernández-Gómez, Francisco José, Ribeiro Do Couto, Bruno, Milanés, M. Victoria, Núñez, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002864/
https://www.ncbi.nlm.nih.gov/pubmed/33803578
http://dx.doi.org/10.3390/ijms22063100
_version_ 1783671554100428800
author Guerrero-Bautista, Rocío
Franco-García, Aurelio
Hidalgo, Juana M.
Fernández-Gómez, Francisco José
Ribeiro Do Couto, Bruno
Milanés, M. Victoria
Núñez, Cristina
author_facet Guerrero-Bautista, Rocío
Franco-García, Aurelio
Hidalgo, Juana M.
Fernández-Gómez, Francisco José
Ribeiro Do Couto, Bruno
Milanés, M. Victoria
Núñez, Cristina
author_sort Guerrero-Bautista, Rocío
collection PubMed
description Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories. Moreover, D3 receptor (D3R) antagonists have recently arisen as a potential treatment for preventing drug relapse. Thus, we have assessed the impact of D3R blockade in the expression of some dopaminergic markers and the activity of the mTOR pathway, which is modulated by D3R, in the BLA and DG during the reinstatement of cocaine-induced conditioned place preference (CPP) evoked by drug priming and social stress. Reinstatement of cocaine CPP paralleled an increasing trend in D3R and dopamine transporter (DAT) levels in the BLA. Social stress, but not drug-induced reactivation of cocaine memories, was prevented by systemic administration of SB-277011-A (a selective D3R antagonist), which was able, however, to impede D3R and DAT up-regulation in the BLA during CPP reinstatement evoked by both stress and cocaine. Concomitant with cocaine CPP reactivation, a diminution in mTOR phosphorylation (activation) in the BLA and DG occurred, which was inhibited by D3R blockade in both nuclei before the social stress episode and only in the BLA when CPP reinstatement was provoked by a cocaine prime. Our data, while supporting a main role for D3R signalling in the BLA in the reactivation of cocaine memories evoked by social stress, indicate that different neural circuits and signalling mechanisms might mediate in the reinstatement of cocaine-seeking behaviours depending upon the triggering stimuli.
format Online
Article
Text
id pubmed-8002864
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80028642021-03-28 Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress Guerrero-Bautista, Rocío Franco-García, Aurelio Hidalgo, Juana M. Fernández-Gómez, Francisco José Ribeiro Do Couto, Bruno Milanés, M. Victoria Núñez, Cristina Int J Mol Sci Article Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories. Moreover, D3 receptor (D3R) antagonists have recently arisen as a potential treatment for preventing drug relapse. Thus, we have assessed the impact of D3R blockade in the expression of some dopaminergic markers and the activity of the mTOR pathway, which is modulated by D3R, in the BLA and DG during the reinstatement of cocaine-induced conditioned place preference (CPP) evoked by drug priming and social stress. Reinstatement of cocaine CPP paralleled an increasing trend in D3R and dopamine transporter (DAT) levels in the BLA. Social stress, but not drug-induced reactivation of cocaine memories, was prevented by systemic administration of SB-277011-A (a selective D3R antagonist), which was able, however, to impede D3R and DAT up-regulation in the BLA during CPP reinstatement evoked by both stress and cocaine. Concomitant with cocaine CPP reactivation, a diminution in mTOR phosphorylation (activation) in the BLA and DG occurred, which was inhibited by D3R blockade in both nuclei before the social stress episode and only in the BLA when CPP reinstatement was provoked by a cocaine prime. Our data, while supporting a main role for D3R signalling in the BLA in the reactivation of cocaine memories evoked by social stress, indicate that different neural circuits and signalling mechanisms might mediate in the reinstatement of cocaine-seeking behaviours depending upon the triggering stimuli. MDPI 2021-03-18 /pmc/articles/PMC8002864/ /pubmed/33803578 http://dx.doi.org/10.3390/ijms22063100 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guerrero-Bautista, Rocío
Franco-García, Aurelio
Hidalgo, Juana M.
Fernández-Gómez, Francisco José
Ribeiro Do Couto, Bruno
Milanés, M. Victoria
Núñez, Cristina
Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress
title Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress
title_full Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress
title_fullStr Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress
title_full_unstemmed Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress
title_short Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress
title_sort distinct regulation of dopamine d3 receptor in the basolateral amygdala and dentate gyrus during the reinstatement of cocaine cpp induced by drug priming and social stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002864/
https://www.ncbi.nlm.nih.gov/pubmed/33803578
http://dx.doi.org/10.3390/ijms22063100
work_keys_str_mv AT guerrerobautistarocio distinctregulationofdopamined3receptorinthebasolateralamygdalaanddentategyrusduringthereinstatementofcocainecppinducedbydrugprimingandsocialstress
AT francogarciaaurelio distinctregulationofdopamined3receptorinthebasolateralamygdalaanddentategyrusduringthereinstatementofcocainecppinducedbydrugprimingandsocialstress
AT hidalgojuanam distinctregulationofdopamined3receptorinthebasolateralamygdalaanddentategyrusduringthereinstatementofcocainecppinducedbydrugprimingandsocialstress
AT fernandezgomezfranciscojose distinctregulationofdopamined3receptorinthebasolateralamygdalaanddentategyrusduringthereinstatementofcocainecppinducedbydrugprimingandsocialstress
AT ribeirodocoutobruno distinctregulationofdopamined3receptorinthebasolateralamygdalaanddentategyrusduringthereinstatementofcocainecppinducedbydrugprimingandsocialstress
AT milanesmvictoria distinctregulationofdopamined3receptorinthebasolateralamygdalaanddentategyrusduringthereinstatementofcocainecppinducedbydrugprimingandsocialstress
AT nunezcristina distinctregulationofdopamined3receptorinthebasolateralamygdalaanddentategyrusduringthereinstatementofcocainecppinducedbydrugprimingandsocialstress