Anushree N Karkhanis1, Jamie H Rose1, Kimberly N Huggins1, Joanne K Konstantopoulos1, Sara R Jones2. 1. Department of Physiology and Pharmacology Translational Center for the Neurobehavioral Study of Alcohol Wake Forest School of Medicine, Winston-Salem, NC, USA. 2. Department of Physiology and Pharmacology Translational Center for the Neurobehavioral Study of Alcohol Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address: srjones@wakehealth.edu.
Abstract
BACKGROUND: Increasing 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. METHODS: The 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/6J mice, 0h and 72h following three weekly cycles (4 days of 16h ethanol vapor/8h room air/day+3 days withdrawal) of CIE vapor exposure. RESULTS: Current results showed that DA release was reduced, uptake rates were increased, and inhibitory D2-type autoreceptor activity was augmented following CIE exposure in mice. CONCLUSIONS: Overall, 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.
BACKGROUND: Increasing 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. METHODS: The 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/6J mice, 0h and 72h following three weekly cycles (4 days of 16h ethanol vapor/8h room air/day+3 days withdrawal) of CIE vapor exposure. RESULTS: Current results showed that DA release was reduced, uptake rates were increased, and inhibitory D2-type autoreceptor activity was augmented following CIE exposure in mice. CONCLUSIONS: Overall, 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.
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