Determining the Impact of Repeated Binge Drinking on Corticostriatal Theta Synchrony

Abstract

The development of alcohol use disorder (AUD) is believed to involve functional adaptations in corticostriatal projections which regulate the reinforcing properties of ethanol (EtOH). To further our understanding of how repeated EtOH consumption impacts the corticostriatal circuit, extracellular electrophysiological recordings (local field potentials; LFPs) were gathered from the nucleus accumbens and prefrontal cortex of female and male C57BL/6J mice voluntarily consuming EtOH or water using ‘drinking-in-the-dark’ (DID) procedures. Mice were given 15 consecutive days of two-hours of access to EtOH (20% v/v), three hours into the dark cycle while LFPs were recorded. To determine the impact of repeated EtOH consumption on neural activity between these brain regions, theta phase-locking value (PLV, a measure of synchrony) was calculated. Specifically, theta PLV was calculated during active drinking periods (bouts) and average PLV during the first bout was compared to the last bout to determine within session changes in synchrony. Results indicated significantly lower PLV during the last bout than the first bout. Additionally, longer bouts predicted lower PLV during the last bout, but not the first bout when mice were consuming EtOH. These results may suggest that alcohol intoxication decreases corticostriatal synchrony over a drinking period. Results considering changes in theta power spectral density (PSD) indicated an increase in PSD when mice were given access to water during the typical EtOH access time following the 15-day EtOH drinking history. This effect was not seen when mice were drinking water prior to EtOH access and may be indicative of a successive negative contrast effect. This work identifies unique functional characteristics of corticostriatal communication associated with binge-like EtOH intake and sets the stage for identifying the biological mechanisms subserving them.