COMT Inhibition Alters Cue-Evoked Oscillatory Dynamics during Alcohol Drinking in the Rat

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

A. M.,Ahn,S.,Rubchinsky,L. L.,Janetsian-Fritz,S. S.,L McCane (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Alterations in the corticostriatal system have been implicated in numerous substance use disorders, includingalcohol use disorder (AUD). Adaptations in this neural system are associated with enhanced drug-seekingbehaviors following exposure to cues predicting drug availability. Therefore, understanding how potentialtreatments alter neural activity in this system could lead to more refined and effective approaches for AUD. Localfield 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 cuesignaled the availability of ethanol (EtOH). On test days, the catechol-o-methyl-transferase (COMT) inhibitortolcapone was administered prior to conditioning. Stimulus-evoked voltage changes were observed following thepresentation of the EtOH cue in both strains and were most pronounced in the PFC of P rats. Phase analyses ofLFPs in the band (5--11 Hz) revealed that PFC-NA synchrony was reduced in P rats relative to Wistars but wasrobustly increased during drinking. Presentation of the cue resulted in a larger phase reset in the PFC of P ratsbut not Wistars, an effect that was attenuated by tolcapone. Additionally, tolcapone reduced cued EtOH intakein P rat but not Wistars. These results suggest a link between corticostriatal synchrony and genetic risk forexcessive drinking. Moreover, inhibition of COMT within these systems may result in reduced attribution ofsalience to reward paired stimuli via modulation of stimulus-evoked changes to cortical oscillations in geneticallysusceptible populations.

Additional Information

Publication

Other

Language: English

Date: 2018

Keywords

alcohol preferring rat; tolcapone; oscillation; prefrontal cortex; nucleus accumbens; alcoholism; alcohol use disorder

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