Prenatal Opioid Exposure Impairs Endocannabinoid and Glutamate Transmission in the Dorsal Striatum.

Autor:	Grecco GG; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202.; Medical Scientist Training Program, Indiana University School of Medicine, Indianapolis, Indiana 46202., Muñoz B; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202., Di Prisco GV; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202., Doud EH; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202.; Center for Proteome Analysis, Indiana University School of Medicine, Indianapolis, Indiana 46202., Fritz BM; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202., Maulucci D; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202., Gao Y; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202., Mosley AL; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202.; Center for Proteome Analysis, Indiana University School of Medicine, Indianapolis, Indiana 46202.; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202., Baucum AJ; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202.; Department of Biology, Indiana University-Purdue University, Indianapolis, Indiana 46202.; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202., Atwood BK; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202 bkatwood@iu.edu.; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2022 Apr 20; Vol. 9 (2). Date of Electronic Publication: 2022 Apr 20 (Print Publication: 2022).
DOI:	10.1523/ENEURO.0119-22.2022
Abstrakt:	The opioid crisis has contributed to a growing population of children exposed to opioids during fetal development; however, many of the long-term effects of opioid exposure on development are unknown. We previously demonstrated that opioids have deleterious effects on endocannabinoid plasticity at glutamate synapses in the dorsal striatum of adolescent rodents, but it is unclear whether prenatal opioid exposure produces similar neuroadaptations. Using a mouse model of prenatal methadone exposure (PME), we performed proteomics, phosphoproteomics, and patch-clamp electrophysiology in the dorsolateral striatum (DLS) and dorsomedial striatum (DMS) to examine synaptic functioning in adolescent PME offspring. PME impacted the proteome and phosphoproteome in a region- and sex-dependent manner. Many proteins and phosphorylated proteins associated with glutamate transmission were differentially abundant in PME offspring, which was associated with reduced glutamate release in the DLS and altered the rise time of excitatory events in the DMS. Similarly, the intrinsic excitability properties of DMS neurons were significantly affected by PME. Last, pathway analyses revealed an enrichment in retrograde endocannabinoid signaling in the DLS, but not in the DMS, of males. Electrophysiology studies confirmed that endocannabinoid-mediated synaptic depression was impaired in the DLS, but not DMS, of PME-males. These results indicate that PME induces persistent neuroadaptations in the dorsal striatum and could contribute to the aberrant behavioral development described in offspring with prenatal opioid exposure. (Copyright © 2022 Grecco et al.)
Databáze:	MEDLINE
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