Detailed Information

Cited 22 time in webofscience Cited 21 time in scopus
Metadata Downloads

Dopaminergic Regulation of Nucleus Accumbens Cholinergic Interneurons Demarcates Susceptibility to Cocaine Addiction

Authors
Lee, Joo HanRibeiro, Efrain A.Kim, JeongseopKo, BumjinKronman, HopeJeong, Yun HaKim, Jong KyoungJanak, Patricia H.Nestler, Eric J.Koo, Ja WookKim, Joung-Hun
Issue Date
Nov-2020
Publisher
ELSEVIER SCIENCE INC
Citation
BIOLOGICAL PSYCHIATRY, v.88, no.10, pp 746 - 757
Pages
12
Journal Title
BIOLOGICAL PSYCHIATRY
Volume
88
Number
10
Start Page
746
End Page
757
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/571
DOI
10.1016/j.biopsych.2020.05.003
ISSN
0006-3223
1873-2402
Abstract
BACKGROUND: Cholinergic interneurons (ChINs) in the nucleus accumbens (NAc) play critical roles in processing information related to reward. However, the contribution of ChINs to the emergence of addiction-like behaviors and its underlying molecular mechanisms remain elusive. METHODS: We employed cocaine self-administration to identify two mouse subpopulations: susceptible and resilient to cocaine seeking. We compared the subpopulations for physiological responses with single-unit recording of NAc ChINs, and for gene expression levels with RNA sequencing of ChINs sorted using fluorescence-activated cell sorting. To provide evidence for a causal relationship, we manipulated the expression level of dopamine D-2 receptor (DRD2) in ChINs in a cell type-specific manner. Using optogenetic activation combined with a double whole-cell recording, the effect of ChIN-specific DRD2 manipulation on each synaptic input was assessed in NAc medium spiny neurons in a pathway-specific manner. RESULTS: Susceptible mice showed higher levels of nosepoke responses under a progressive ratio schedule, and impairment in extinction and punishment procedures. DRD2 was highly abundant in the NAc ChINs of susceptible mice. Elevated abundance of DRD2 in NAc ChINs was sufficient and necessary to express high cocaine motivation, putatively through reduction of ChIN activity during cocaine exposure. DRD2 overexpression in ChINs mimicked cocaine-induced effects on the dendritic spine density and the ratios of excitatory inputs between two distinct medium spiny neuron cell types, while DRD2 depletion precluded cocaine-induced synaptic plasticity. CONCLUSIONS: These findings provide a molecular mechanism for dopaminergic control of NAc ChINs that can control the susceptibility to cocaine-seeking behavior.
Files in This Item
Appears in
Collections
연구본부 > 퇴행성 뇌질환 연구그룹 > 1. Journal Articles
연구본부 > 정서·인지 질환 연구그룹 > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Altmetrics

Total Views & Downloads

BROWSE