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Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking

The time-dependent increase in cue-triggered opioid seeking, termed “incubation of opioid craving,” is modeled in rodents by examining responding for opioid-associated cues after a period of forced abstinence. With opioid drugs, withdrawal symptoms may heighten cue reactivity by recruiting brain sys...

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Autores principales: Gyawali, Utsav, Martin, David A., Sulima, Agnieszka, Rice, Kenner C., Calu, Donna J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493668/
https://www.ncbi.nlm.nih.gov/pubmed/33088264
http://dx.doi.org/10.3389/fnbeh.2020.00153
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author Gyawali, Utsav
Martin, David A.
Sulima, Agnieszka
Rice, Kenner C.
Calu, Donna J.
author_facet Gyawali, Utsav
Martin, David A.
Sulima, Agnieszka
Rice, Kenner C.
Calu, Donna J.
author_sort Gyawali, Utsav
collection PubMed
description The time-dependent increase in cue-triggered opioid seeking, termed “incubation of opioid craving,” is modeled in rodents by examining responding for opioid-associated cues after a period of forced abstinence. With opioid drugs, withdrawal symptoms may heighten cue reactivity by recruiting brain systems involved in both reward seeking and stress responses. Corticotropin releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) is a critical driver of stress-induced relapse to drug seeking. Here, we sought to determine whether BNST CRF receptor 1 (CRFR1) signaling drives incubation of opioid craving in opioid dependent and non-dependent rats. First, we tested whether BNST CRFR1 signaling drives incubation of opioid craving in rats with short-access fentanyl self-administration experience (2.5 μg/kg/infusion, 3 h/day for 10 days). On Day 1 of forced abstinence, we gave bilateral intra-BNST vehicle injections to all rats and measured lever responding for opioid cues in the absence of fentanyl infusions. On Day 30 of forced abstinence, we gave an identical test after bilateral intra-BNST injections of vehicle or CRFR1 receptor antagonist, R121919 (1 μg/0.3 μL/hemisphere). Vehicle treated rats showed greater responding for opioid associated cues on Day 30 relative to Day 1, and this incubation effect was prevented by intra-BNST R121919 on Day 30. Next, we incorporated an opioid-dependence procedure to investigate whether BNST CRFR1 signaling drives opioid cue-reactivity to a greater extent in opioid-dependent relative to non-dependent rats. We trained rats to self-administer fentanyl for 5 days before initiating the dependence phase and resuming daily fentanyl self-administration sessions for 10 days. We gave intra-BNST R121919 or vehicle injections before testing during acute (Day 5) or protracted (Day 30) withdrawal. During acute withdrawal, antagonizing BNST CRFR1 decreased the number of press bouts without affecting bout size or duration. These patterns of responding with R121919 treatment resulted in less fentanyl-associated conditioned reinforcement during test. Together, these findings suggest a role for BNST CRFR1 signaling in driving cue-reinforced opioid seeking after periods of forced abstinence.
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spelling pubmed-74936682020-10-20 Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking Gyawali, Utsav Martin, David A. Sulima, Agnieszka Rice, Kenner C. Calu, Donna J. Front Behav Neurosci Neuroscience The time-dependent increase in cue-triggered opioid seeking, termed “incubation of opioid craving,” is modeled in rodents by examining responding for opioid-associated cues after a period of forced abstinence. With opioid drugs, withdrawal symptoms may heighten cue reactivity by recruiting brain systems involved in both reward seeking and stress responses. Corticotropin releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) is a critical driver of stress-induced relapse to drug seeking. Here, we sought to determine whether BNST CRF receptor 1 (CRFR1) signaling drives incubation of opioid craving in opioid dependent and non-dependent rats. First, we tested whether BNST CRFR1 signaling drives incubation of opioid craving in rats with short-access fentanyl self-administration experience (2.5 μg/kg/infusion, 3 h/day for 10 days). On Day 1 of forced abstinence, we gave bilateral intra-BNST vehicle injections to all rats and measured lever responding for opioid cues in the absence of fentanyl infusions. On Day 30 of forced abstinence, we gave an identical test after bilateral intra-BNST injections of vehicle or CRFR1 receptor antagonist, R121919 (1 μg/0.3 μL/hemisphere). Vehicle treated rats showed greater responding for opioid associated cues on Day 30 relative to Day 1, and this incubation effect was prevented by intra-BNST R121919 on Day 30. Next, we incorporated an opioid-dependence procedure to investigate whether BNST CRFR1 signaling drives opioid cue-reactivity to a greater extent in opioid-dependent relative to non-dependent rats. We trained rats to self-administer fentanyl for 5 days before initiating the dependence phase and resuming daily fentanyl self-administration sessions for 10 days. We gave intra-BNST R121919 or vehicle injections before testing during acute (Day 5) or protracted (Day 30) withdrawal. During acute withdrawal, antagonizing BNST CRFR1 decreased the number of press bouts without affecting bout size or duration. These patterns of responding with R121919 treatment resulted in less fentanyl-associated conditioned reinforcement during test. Together, these findings suggest a role for BNST CRFR1 signaling in driving cue-reinforced opioid seeking after periods of forced abstinence. Frontiers Media S.A. 2020-08-28 /pmc/articles/PMC7493668/ /pubmed/33088264 http://dx.doi.org/10.3389/fnbeh.2020.00153 Text en Copyright © 2020 Gyawali, Martin, Sulima, Rice and Calu. https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Neuroscience
Gyawali, Utsav
Martin, David A.
Sulima, Agnieszka
Rice, Kenner C.
Calu, Donna J.
Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking
title Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking
title_full Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking
title_fullStr Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking
title_full_unstemmed Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking
title_short Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking
title_sort role of bnst crfr1 receptors in incubation of fentanyl seeking
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493668/
https://www.ncbi.nlm.nih.gov/pubmed/33088264
http://dx.doi.org/10.3389/fnbeh.2020.00153
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