title: Suppressive regulation of lateral inhibition between medium spiny neurons via dopamine D1receptors in the rat nucleus accumbens shell.
abstract: The nucleus accumbens (NAc) shell is closely associated with reward, psychiatric disorders (depression or schizophrenia), and drug abuse. Dopamine, released from the ventral tegmental area, is involved in these physiological functions and pathophysiological changes of NAc shell. Medium spiny neurons (MSNs), which are only GABAergic projection neurons in NAc, also innervate adjacent MSNs, forming the lateral inhibition network. Previous studies demonstrate that dopamine suppresses the lateral inhibition via D2-like (D2and D3) receptors. However, the regulation to MSN-MSN synaptic transmission via D1receptors remained unclear. In present study, aiming to reveal this issue, we examined the effects of the potent dopamine D1receptor selective agonist SKF82958 on unitary IPSCs (uIPSCs) between two MSNs. SKF82958 (10μM) decreased the amplitude of uIPSCs in about half of MSNs. The actions of SKF82958 was eliminated by pre-application of SCH23390 (1μM), a dopamine D1receptor selective antagonist. These results suggest that lateral inhibition between MSNs was suppressed via the activation of D1receptors. Taken our previous findings, dopamine exclusively abolish the lateral inhibition in a stepwise pattern: (1) at low concentration of dopamine, only D3receptors take part in the regulation of MSN-MSN synaptic transmissions, (2) dopamine concentration becomes higher, D2receptors become involved in the suppression of lateral inhibition, and (3) at the maximal activity of the mesolimbic dopaminergic pathway, all dopamine receptor subtypes (i.e., D1, D2, and D3) are recruited for disinhibition of MSN activities.
authors: Department of Neurophysiology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa 769-2193, Japan. Electronic address: kohnomi@kph.bunri-u.ac.jp.
authors: Shuntaro
authors: S
authors: Kohnomi
authors: Department of Pharmacology, Dental Research Center, Nihon University School of Dentistry, Tokyo 101-8310, Japan.
authors: Katsuko
authors: K
authors: Ebihara
authors: Department of Pharmacology, Dental Research Center, Nihon University School of Dentistry, Tokyo 101-8310, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry, Tokyo 101-8310, Japan; RIKEN Center for Molecular Imaging Science, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors: Masayuki
authors: M
authors: Kobayashi
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D005260:Female; D008297:Male; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; C071262:SK&F 82958
keywords: Dopamine; Lateral inhibition; Nucleus accumbens shell; SKF82958; Unitary IPSC