Impact of Voluntary Alcohol Consumption on Corticostriatal Plasticity in Rats.

Alcohol use disorder (AUD) is a chronic relapsing disorder that is characterized by loss of control over alcohol consumption. Loss of control over alcohol use has been proposed to be mediated by a combination of habitual substance use, caused by functional changes in the dorsolateral striatum (DLS), and breakdown of cognitive control over alcohol use, subserved by cortical areas. We have previously shown that a subgroup of Lister Hooded rats develops loss of control over alcohol seeking after voluntary intermittent-every-other-day consumption of alcohol. The aim of this study was therefore to determine the effects of long-term voluntary alcohol consumption on sensorimotor cortical inputs to the DLS in subgroups of rats that had consumed low versus high amounts of alcohol. To that end, optogenetics and patch-clamp electrophysiology were combined to investigate functional changes in cortical projections to the DLS after 8 weeks of voluntary alcohol consumption. We observed lower AMPA/NMDA ratios in alcohol-consuming rats, indicative of long-term depression of this projection upon exposure to alcohol. We observed a reduced coefficient of variance and, selectively in high alcohol drinking rats, an increase in paired-pulse facilitation. This indicates that voluntary alcohol consumption induces both post- and presynaptic changes in the sensorimotor cortical inputs to the DLS. These findings show that alcohol consumption affects corticostriatal plasticity, which might contribute to the development of AUD.