Chronic intermittent ethanol exposure differentially alters the excitability of neurons in the orbitofrontal cortex and basolateral amygdala that project to the dorsal striatum

Neuropharmacology. 2023 May 1:228:109463. doi: 10.1016/j.neuropharm.2023.109463. Epub 2023 Feb 13.


Alcohol use disorder is associated with altered neuron function including those in orbitofrontal cortex (OFC) and basolateral amygdala (BLA) that send glutamatergic inputs to areas of the dorsal striatum (DS) that mediate goal and habit directed actions. Previous studies reported that chronic intermittent (CIE) exposure to ethanol alters the electrophysiological properties of OFC and BLA neurons, although projection targets for these neurons were not identified. In this study, we used male and female mice and recorded current-evoked spiking of retrobead labeled DS-projecting OFC and BLA neurons in the same animals following air or CIE treatment. DS-projecting OFC neurons were hyperexcitable 3- and 7-days following CIE exposure and spiking returned to control levels after 14 days of withdrawal. In contrast, firing was decreased in DS-projecting BLA neurons at 3-days withdrawal, increased at 7- and 14-days and returned to baseline at 28 days post-CIE. CIE exposure enhanced the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) of DS-projecting OFC neurons but had no effect on inhibitory postsynaptic currents (sIPSCs). In DS-projecting BLA neurons, the amplitude and frequency of sIPSCs was enhanced 3 days post-CIE with no change in sEPSCs while at 7-days post-withdrawal, sEPSC amplitude and frequency were increased and sIPSCs had returned to normal. Finally, in CIE-treated mice, acute ethanol no longer inhibited spike firing of DS-projecting OFC and BLA neurons. Overall, these results suggest that CIE-induced changes in the excitability of DS-projecting OFC and BLA neurons could underlie deficits in behavioral control often observed in alcohol-dependent individuals.

Keywords: Basolateral amygdala; Chronic ethanol exposure; Dorsal medial striatum; Intrinsic excitability; Orbitofrontal cortex; Spontaneous postsynaptic currents.

Publication types

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

MeSH terms

  • Alcoholism*
  • Animals
  • Basolateral Nuclear Complex*
  • Ethanol
  • Female
  • Male
  • Mice
  • Neurons
  • Prefrontal Cortex


  • Ethanol