JournalFrontiers in Behavioral Neuroscience
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractThe 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.
DescriptionIn the original article, there were mistakes in Figures 2 and 3, and Supplementary Figure 3, as published. The lines in Figure 2C, Figures 3A,B and D, and Supplementary Figure 3, were erroneously connecting the individual data points and have been removed. The individual data is still represented in these figures and is identical to the published data but is no longer connected with lines. The corrected Figure 2, Figure 3, and Supplementary Figure 3 appear in https://doi.org/10.3389/fnbeh.2021.660759.
Rights/TermsCopyright © 2020 Gyawali, Martin, Sulima, Rice and Calu.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15892
- Maladaptive behavioral regulation in alcohol dependence: Role of kappa-opioid receptors in the bed nucleus of the stria terminalis.
- Authors: Erikson CM, Wei G, Walker BM
- Issue date: 2018 Sep 15
- Anxiogenic effects of CGRP within the BNST may be mediated by CRF acting at BNST CRFR1 receptors.
- Authors: Sink KS, Chung A, Ressler KJ, Davis M, Walker DL
- Issue date: 2013 Apr 15
- Time-dependent changes in extinction behavior and stress-induced reinstatement of drug seeking following withdrawal from heroin in rats.
- Authors: Shalev U, Morales M, Hope B, Yap J, Shaham Y
- Issue date: 2001 Jun
- A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking.
- Authors: Erb S, Stewart J
- Issue date: 1999 Oct 15
- β-endorphin via the delta opioid receptor is a major factor in the incubation of cocaine craving.
- Authors: Dikshtein Y, Barnea R, Kronfeld N, Lax E, Roth-Deri I, Friedman A, Gispan I, Elharrar E, Levy S, Ben-Tzion M, Yadid G
- Issue date: 2013 Nov