Long-term subregion-specific encoding of enhanced ethanol intake by D1DR medium spiny neurons of the nucleus accumbens

Addict Biol. 2018 Mar;23(2):689-698. doi: 10.1111/adb.12526. Epub 2017 Jun 28.

Abstract

The nucleus accumbens (NAc) is a critical component of the mesocorticolimbic system and is involved in mediating the motivational and reinforcing aspects of ethanol consumption. Chronic intermittent ethanol (CIE) exposure is a reliable model to induce ethanol dependence and increase volitional ethanol consumption in mice. Following a CIE-induced escalation of ethanol consumption, NMDAR (N-methyl-D-aspartate receptor)-dependent long-term depression in D1 dopamine receptor expressing medium spiny neurons of the NAc shell was markedly altered with no changes in plasticity in D1 dopamine receptor medium spiny neurons from the NAc core. This disruption of plasticity persisted for up to 2 weeks after cessation of ethanol access. To determine if changes in AMPA receptor (AMPAR) composition contribute to this ethanol-induced neuroadaptation, we monitored the rectification of AMPAR excitatory postsynaptic currents (EPSCs). We observed a marked decrease in the rectification index in the NAc shell, suggesting the presence of GluA2-lacking AMPARs. There was no change in the amplitude of spontaneous EPSCs (sEPSCs), but there was a transient increase in sEPSC frequency in the NAc shell. Using the paired pulse ratio, we detected a similar transient increase in the probability of neurotransmitter release. With no change in sEPSC amplitude, the change in the rectification index suggests that GluA2-containing AMPARs are removed and replaced with GluA2-lacking AMPARs in the NAc shell. This CIE-induced alteration in AMPAR subunit composition may contribute to the loss of NMDAR-dependent long-term depression in the NAc shell and therefore may constitute a critical neuroadaptive response underlying the escalation of ethanol intake in the CIE model.

Keywords: CIE; LTD; alcohol; plasticity; striatum.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking
  • Animals
  • Central Nervous System Depressants / administration & dosage*
  • Ethanol / administration & dosage*
  • Excitatory Postsynaptic Potentials*
  • Long-Term Synaptic Depression*
  • Mice
  • Neuronal Plasticity
  • Neurons / metabolism*
  • Nucleus Accumbens / metabolism*
  • Patch-Clamp Techniques
  • Receptors, AMPA / metabolism*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, N-Methyl-D-Aspartate / isolation & purification
  • Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

  • Central Nervous System Depressants
  • Drd1 protein, mouse
  • Receptors, AMPA
  • Receptors, Dopamine D1
  • Receptors, N-Methyl-D-Aspartate
  • Ethanol
  • glutamate receptor ionotropic, AMPA 2