used here, a down-regulation of α4 subunits, which would be predicted to reduce inhibition in some neurons within the shell, produces a similar behavioral effect as a general inhibition of GABAARs (and the neurons expressing these receptors). This difference suggests that the effects of down-regulating the GABAAR α4 subunit in particular on ethanol intake may not result from the disinhibition of the circuits identified by Kelley and colleagues in control of consumption of palatable substances in general (Baldo & Kelley 2007). It is possible that these differences could arise from differences in the effects on cellular function when altering both extrasynaptic and synaptic GABA transmission, rather than just extrasynaptic. Alternatively, α4 down-regulation and muscimol infusion could exert distinct effects on ethanol intake if α4-containing receptors were expressed only on a subset of neurons within the NAc shell, e.g. in only the direct or indirect pathway neurons. Future studies are required to determine the specific physiological effects of α4-containing GABAARs in the NAc medial shell.
