Selective modulation of GABAergic tonic current by dopamine in the nucleus accumbens of alcohol-dependent rats.

Autor:	Liang J; Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, California; and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California., Marty VN; Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, California; and., Mulpuri Y; Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, California; and., Olsen RW; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California., Spigelman I; Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, California; and igor@ucla.edu.
Jazyk:	angličtina
Zdroj:	Journal of neurophysiology [J Neurophysiol] 2014 Jul 01; Vol. 112 (1), pp. 51-60. Date of Electronic Publication: 2014 Apr 09.
DOI:	10.1152/jn.00564.2013
Abstrakt:	The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Alterations in glutamatergic and GABAergic signaling were recently demonstrated in the NAcc of rats after chronic intermittent ethanol (CIE) treatment, a model of alcohol dependence. Here we studied dopamine (DA) modulation of GABAergic signaling and how this modulation might be altered by CIE treatment. We show that the tonic current (I(tonic)) mediated by extrasynaptic γ-aminobutyric acid type A receptors (GABA(A)Rs) of medium spiny neurons (MSNs) in the NAcc core is differentially modulated by DA at concentrations in the range of those measured in vivo (0.01-1 μM), without affecting the postsynaptic kinetics of miniature inhibitory postsynaptic currents (mIPSCs). Use of selective D1 receptor (D1R) and D2 receptor (D2R) ligands revealed that I(tonic) potentiation by DA (10 nM) is mediated by D1Rs while I(tonic) depression by DA (0.03-1 μM) is mediated by D2Rs in the same MSNs. Addition of guanosine 5'-O-(2-thiodiphosphate) (GDPβS) to the recording pipettes eliminated I(tonic) decrease by the selective D2R agonist quinpirole (5 nM), leaving intact the quinpirole effect on mIPSC frequency. Recordings from CIE and vehicle control (CIV) MSNs during application of D1R agonist (SKF 38393, 100 nM) or D2R agonist (quinpirole, 2 nM) revealed that SKF 38393 potentiated I(tonic) to the same extent, while quinpirole reduced I(tonic) to a similar extent, in both groups of rats. Our data suggest that the selective modulatory effects of DA on I(tonic) are unaltered by CIE treatment and withdrawal. (Copyright © 2014 the American Physiological Society.)
Databáze:	MEDLINE
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