Effects of chronic ethanol consumption on the expression of GLT-1 and neuroplasticity-related proteins in the nucleus accumbens of alcohol-preferring rats

Brain Res Bull. 2020 Dec;165:272-280. doi: 10.1016/j.brainresbull.2020.10.012. Epub 2020 Oct 16.


Chronic ethanol exposure induces impairments in CNS excitatory and inhibitory activity. These impairments are associated with glutamatergic dysfunction, including altered neuroplasticity. This study examined the effects of 6-week ethanol (15% and 30% v/v) consumption, by male alcohol-preferring P rats, on protein expression associated with neuroplasticity and glutamate transporter-1 (GLT-1) function. The latter regulates intra- and extra-synaptic glutamate levels. We focused on the shell and core subregions of the nucleus accumbens (Acb); i.e., shell (AcbSh) and core (AcbCo), for these measures. Chronic ethanol exposure increased the expression of BDNF, Arc and phosphorylated (p)-post-synaptic density protein-95 (p-PSD-95) in the AcbSh of P rats. Moreover, the ratio of phospho-neuronal nitric oxide synthase (p-nNOS) to total nNOS was also increased in the AcbSh. These changes in BDNF, Arc and p-nNOS/nNOS ratio were not observed in the AcbCo. Furthermore, chronic ethanol consumption reduced GLT-1 expression in the AcbSh. Alternatively, treatment with ceftriaxone (CEF), a known GLT-1 upregulator, abolished the effect of chronic ethanol consumption on BDNF expression in the AcbSh. Overall, the present findings confirm that chronic ethanol consumption modulates activity-associated synaptic proteins, including BDNF, Arc and nNOS in a subregion-specific (i.e., in the AcbSh but not AcbCo) manner. Thus, alterations in mesocorticolimbic glutamatergic homeostasis and neuroplasticity are possible functional targets for the treatment of alcohol use disorders.

Keywords: Arc; BDNF; Ethanol dependence; GLT-1; glutamate; nNOS; nucleus accumbens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / metabolism*
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Disks Large Homolog 4 Protein / metabolism
  • Ethanol / administration & dosage*
  • Excitatory Amino Acid Transporter 2 / metabolism*
  • Male
  • Neuronal Plasticity / physiology
  • Nitric Oxide Synthase Type I / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Phosphorylation / drug effects
  • Rats


  • Brain-Derived Neurotrophic Factor
  • Disks Large Homolog 4 Protein
  • Excitatory Amino Acid Transporter 2
  • Slc1a2 protein, rat
  • Ethanol
  • Nitric Oxide Synthase Type I