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2014 Abstracts

Ethanol Inhibits Dopamine Release at Terminals in the Nucleus Accumbens Via GABA Receptors

Eliza Warren, Brigham Young University

Life Sciences

We have previously demonstrated that ethanol inhibition of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), and γ-aminobutyric acid (GABA) neurons in other ethanol-sensitive brain areas, is mediated by GABA(B) receptors. The aim of this study was to evaluate the involvement of GABA and glutamate (GLU), and in particular GABA(A), GABA(B) and NMDA receptors, in mediating ethanol inhibition of dopamine (DA) release in the NAc. Using fast scan cyclic voltammetry (FSCV), we evaluated the effects of ethanol on DA release in the NAc core of C57/BL6 and CD-1 mice. In the slice preparation, local stimulation evoked robust, frequency-dependent DA release in the NAc, with maximal release at 20 Hz. Ethanol decreased DA release with an IC50 of 60 mM in C57Bl6 mice. In anesthetized C57BL6 mice, ethanol decreased DA release with an IC50 of 2.0 g/kg. Superfusion of the GABA(B) receptor antagonist CGP55845 enhanced DA release 85%, while neither the GABA(A) receptor antagonist bicuculline, the GABA(A) receptor agonist muscimol, the GABA(B) receptor agonist baclofen, nor the NMDA GLU antagonist APV significantly affected DA release. CGP55845 blocked ethanol inhibition of DA release, while neither bicuculline nor APV altered ethanol’s effects. GABA inhibited DA release at 0.5-10 uM but not at 0.1-1 mM. Compared to ethanol effects on DA release in C57BL6 mice, CD-1 GAD GFP knock-in mice, which only express GAD at 50% levels, were significantly less sensitive to ethanol. As DA release was sensitive to low concentrations of GABA, CGP55845 may act as a GABA(A) rho receptor antagonist, and neither bicuculline nor baclofen had any effect on DA release, ethanol may be acting on extrasynaptic GABA(A) rho receptors on DA terminals to inhibit DA release in the NAc.