Chronic intermittent ethanol exposure reduces presynaptic dopamine neurotransmission in the mouse nucleus accumbens

• Chronic intermittent ethanol (CIE) exposure results in decreased dopamine release in the nucleus accumbens of mice. This decrease in stimulated dopamine release was observed at the 0 h off time point (immediately after cessation of CIE exposure) and at the 72 h off time point (after 72 h of withdrawal).
• CIE exposure increased dopamine uptake rate at the dopamine terminals at the 0 h and 72 h off time points.
• The current data showed that potency of quinpirole increased during the 0 h off time point. However no significant difference between quinpirole potency was found between the air-exposed control animals and CIE exposed animals at the 72 h off time point. These data suggest that D2 receptors were supersensitive transiently after CIE exposure.

BackgroundIncreasing evidence suggests that chronic ethanol exposure decreases dopamine (DA) neurotransmission in the nucleus accumbens (NAc), contributing to a hypodopaminergic state during withdrawal. However, few studies have investigated adaptations in presynaptic DA terminals after chronic intermittent ethanol (CIE) exposure. In monkeys and rats, chronic ethanol exposure paradigms have been shown to increase DA uptake and D2 autoreceptor sensitivity.MethodsThe current study examined the effects of ethanol on DA terminals in CIE exposed mice during two time-points after the cessation of CIE exposure. DA release and uptake were measured using fast scan cyclic voltammetry in NAc core slices from C57BL/6 J mice, 0 h and 72 h following three weekly cycles (4 days of 16 h ethanol vapor/8 h room air/day + 3 days withdrawal) of CIE vapor exposure.ResultsCurrent results showed that DA release was reduced, uptake rates were increased, and inhibitory D2-type autoreceptor activity was augmented following CIE exposure in mice.ConclusionsOverall, these CIE-induced adaptations in the accumbal DA system reduce DA signaling and therefore reveal several potential mechanisms contributing to a functional hypodopaminergic state during alcohol withdrawal.