nAChR-mediated synaptic plasticity. In the NAc, synapses can express both LTP and LTD (Kombian and Malenka, 1994) but mainly NMDAR-dependent LTD has been demonstrated following administration of psychostimulants, such as cocaine and amphetamine, which involves the endocytosis of AMPARs. Although in some situations ethanol has been shown to inhibit NMDAR activity and associated plasticity (Blitzer et al., 1990), activation of DA D1 receptors will diminish ethanol's inhibition of NMDARs thus promoting reinforcement and plasticity in the NAc (Maldve et al., 2002). Ethanol treatment (50 mM) has been shown to cause a short-term depression of the striatal output and this effect is sensitive to nAChR antagonists, MEC (10 μM) and MLA (40 nM), which block the depression of synaptic output (Adermark et al., 2011).
