Our data demonstrate that previous LPS exposure leads to a reduction in the basal firing activity of VTA dopamine neurons. Low basal dopamine levels in the nucleus accumbens (NAc), the major dopamine neuron projection area, have been associated with high ethanol preference and consumption in both mice and rats (George et al., 1995; McBride et al., 1995). Furthermore, profound decreases in VTA dopamine neuron activity and NAc dopamine release have been reported in rats withdrawn from repeated ethanol exposure (Diana et al., 1993). Interestingly, these ethanol-dependent rats consume ethanol until NAc dopamine levels are restored to control levels (Weiss et al., 1996). Therefore, the reduced dopamine neuron activity observed after LPS treatment may mimic the ethanol-dependent state that drives excessive ethanol consumption. In this regard, it is of note that reduced dopamine release in the striatum has also been reported in detoxified alcoholics (Martinez et al., 2005; Volkow et al., 2007).
