Figure 8.

Schematic diagram summarizes the effects of chronic ethanol consumption on GLT-1, NO pathway, BDNF, and Arc expression in the AcbSh. Chronic ethanol consumption increases synaptic glutamate concentration mainly due to downregulation of GLT-1 (both GLT-1a and GLT-1b isoforms) and cystine/glutamate exchanger transporter (xCT) expression (Alhaddad et al., 2014a; Das et al., 2015). Chronic ethanol consumption also increases NO system activity, BDNF-Arc expression and PSD-95. NO regulates the incorporation of postsynaptic GluA1 subunit of AMPA receptors probably through CREB-BDNF-Arc pathway and ubiquitination of PSD-95. In addition, chronic ethanol exposure was associated with increases in the inflammatory response through upregulation of inflammatory mediators such as high mobility group box 1 (HMGB1), a receptor for advanced glycation end products (RAGE) and TNF-α (Alasmari et al., 2020).