TY - JOUR T1 - COMT inhibition alters cued-evoked oscillatory dynamics during alcohol drinking in the rat JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0326-18.2018 SP - ENEURO.0326-18.2018 AU - A. M. McCane AU - S. Ahn AU - L. L. Rubchinsky AU - S.S. Janetsian-Fritz AU - D.N. Linsenbardt AU - C. L. Czachowski AU - C. C. Lapish Y1 - 2018/10/12 UR - http://www.eneuro.org/content/early/2018/10/12/ENEURO.0326-18.2018.abstract N2 - Background: Alterations in the corticostriatal system have been implicated in numerous substance use disorders, including alcohol use disorder (AUD). Adaptations in this neural system are associated with enhanced drug-seeking behaviors following exposure to cues predicting drug availability. Therefore, understanding how potential treatments alter neural activity in this system could lead to more refined and effective approaches for AUD. Methods: Local field potentials (LFPs) were acquired simultaneously in the prefrontal cortex (PFC) and nucleus accumbens (NA) of both alcohol preferring (P) and Wistar rats engaged in a Pavlovian conditioning paradigm wherein a light cue signaled the availability of ethanol. On test days, the COMT inhibitor tolcapone was administered prior to conditioning. Results: Stimulus-evoked voltage changes were observed following the presentation of the ethanol cue in both strains, and were most pronounced in the PFC of P rats. Phase analyses of LFPs in the theta band (5-11 Hz) revealed that PFC-NA synchrony was reduced in P rats relative to Wistars, but was robustly increased during drinking. Presentation of the cue resulted in a larger phase reset in the PFC of P rats but not Wistars, an effect that was attenuated by tolcapone. Additionally, tolcapone reduced cued ethanol intake in P rat but not Wistars. Conclusions: These results suggest a link between corticostriatal synchrony and genetic risk for excessive drinking. Moreover, inhibition of COMT within these systems may result in reduced attribution of salience to reward paired stimuli via modulation of stimulus-evoked changes to cortical oscillations in genetically susceptible populations.Significance statement Alcoholism is highly heritable and genetic vulnerability is associated with increased likelihood of alcohol-use related problems. Presentation of environmental stimuli paired with alcohol are capable of inducing craving and relapse in alcohol dependent individuals. The work described here using a rodent model of cued ethanol availability suggests that altered corticostriatal activity may be associated with genetic vulnerability to abuse alcohol. Additionally, our data suggest that inhibition of the COMT enzyme activity may reduce the influence that alcohol-conditioned stimuli elicit on behavior, resulting in a reduction of cued alcohol seeking in genetically susceptible individuals. ER -