Opioid withdrawal involves the manifestation of motivational and somatic symptoms. However, the brain structures that are involved in the expression of different opioid withdrawal signs remain unclear. We induced opioid dependence by repeatedly injecting escalating heroin doses in male and female C57BL/6J mice. We assessed hyperalgesia during spontaneous heroin withdrawal and somatic signs of withdrawal that was precipitated by the preferential μ-opioid receptor antagonist naloxone. Heroin-treated mice exhibited significantly higher hyperalgesia and somatic signs than saline-treated mice. Following behavioral assessment, we measured regional changes in brain activity by automated the counting of c-Fos expression (a marker of cellular activity). Using Principal Component Analysis, we determined the association between behavior (hyperalgesia and somatic signs of withdrawal) and c-Fos expression in different brain regions. Hyperalgesia was associated with c-Fos expression in the lateral hypothalamus, central nucleus of the amygdala, ventral tegmental area, parabrachial nucleus, dorsal raphe (DR), and locus coeruleus (LC). Somatic withdrawal was associated with c-Fos expression in the paraventricular nucleus of the thalamus, lateral habenula, DR, and LC. Thus, hyperalgesia and somatic withdrawal signs were each associated with c-Fos expression in unique sets of brain areas. The expression of c-Fos in the DR and LC was associated with both hyperalgesia and somatic withdrawal. Understanding common neurobiological mechanisms of acute and protracted opioid withdrawal may help identify new targets for treating this salient aspect of opioid use disorder.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.