title: Optogenetics reveals a role for accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization.
abstract: Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have been proposed to contribute to drug-mediated addictive behaviors. Here we have used an optogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cre transgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2R-MSNs form local inhibitory circuits, because photostimulation of D2R-MSN evoked inhibitory postsynaptic currents (IPSCs) in neighboring MSNs. Photostimulation of NAc D2R-MSN in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. However, photostimulation during the drug withdrawal period attenuated expression of cocaine-induced behavioral sensitization. These results show that D2R-MSNs of NAc play a key role in withdrawal-induced plasticity and may contribute to relapse after cessation of drug abuse.
authors.affiliation: Department of Life Sciences, Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology Korea University, Seoul, South Korea.
authors.forename: Shelly Sooyun
authors.initials: SS
authors.lastname: Song
authors.affiliation: Department of Life Sciences, Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology Korea University, Seoul, South Korea.
authors.forename: Byeong Jun
authors.initials: BJ
authors.lastname: Kang
authors.affiliation: Center for Functional Connectomics (CFC) KIST, Seoul, South Korea ; Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore ; Institute of Molecular and Cell Biology Singapore, Singapore.
authors.forename: Lei
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Life Sciences, Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology Korea University, Seoul, South Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology Korea University, Seoul, South Korea.
authors.forename: Hye-Ri
authors.initials: HR
authors.lastname: Sim
authors.affiliation: Department of Life Sciences, Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology Korea University, Seoul, South Korea.
authors.forename: Tae Hyong
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology Korea University, Seoul, South Korea.
authors.forename: Sehyoun
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Life Sciences, Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology Korea University, Seoul, South Korea.
authors.forename: Bong-June
authors.initials: BJ
authors.lastname: Yoon
authors.affiliation: Center for Functional Connectomics (CFC) KIST, Seoul, South Korea ; Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore ; Institute of Molecular and Cell Biology Singapore, Singapore.
authors.forename: George J
authors.initials: GJ
authors.lastname: Augustine
authors.affiliation: Department of Life Sciences, Molecular Neurobiology Laboratory, School of Life Sciences and Biotechnology Korea University, Seoul, South Korea.
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Baik
keywords: cocaine; dopamine D2 receptors; drug addiction; medium spiny neurons; optogenetics