Inhibition of Catechol-O-methyltransferase Does Not Alter Effort-Related Choice Behavior in a Fixed Ratio/Concurrent Chow Task in Male Mice

Abstract

Effort-related choice (ERC) tasks allow animals to choose between high-value reinforcers that require high effort to obtain and low-value/low-effort reinforcers. Dopaminergic neuromodulation regulates ERC behavior. The enzyme catechol-O-methyltransferase (COMT) metabolizes synaptically-released dopamine. COMT is the predominant regulator of dopamine turnover in regions of the brain with low levels of dopamine transporters (DATs), including the prefrontal cortex (PFC). Here, we evaluated the effects of the COMT inhibitor tolcapone on ERC performance in a touchscreen-based fixedratio/concurrent chow task in male mice. In this task, mice were given the choice between engaging in a fixed number of instrumental responses to acquire a strawberry milk reward and consuming standard lab chow concurrently available on the chamber floor. We found no significant effects of tolcapone treatment on either strawberry milk earned or chow consumed compared to vehicle treatment. In contrast, we found that haloperidol decreased instrumental responding for strawberry milk and increased chow consumption as seen in previously published studies. These data suggest that COMT inhibition does not significantly affect effort-related decision making in a fixedratio/concurrent chow task in male mice.

Electrophysiological correlates of attention in the locus coeruleus - anterior cingulate cortex circuit during the rodent continuous performance test

“…In contrast to activity in the LC, delta and theta power in the ACC LFP distinguishes between hits and false alarms even when mice have not yet learned the task rule. Indeed, response time differences in this study demonstrate a dissociation between visual discrimination and behavioral choice, indicating that mice discriminate between the target and non-target well in advance of learning to respond differently to the two [78]. Increased ACC power tracks this visual discrimination across orthogonal learning states, consistent with a role for the ACC in attention-related sensory processing [79,80] and decision making during both periods of certainty and uncertainty [81,82].…”

Catechol-O-methyltransferase activity does not influence emotional processing in men

“…Given these findings, COMT inhibitors with more optimal properties are under active development for the treatment of cognitive dysfunction in schizophrenia and other disorders ( Byers et al, 2020 ; Su et al, 2021 ). However, COMT’s significance for clinically relevant domains other than executive cognition remains largely unexplored ( DeBrosse et al, 2020 ; Korn et al, 2021 ; Tunbridge et al, 2012 ) and may have significance for understanding potential additional indications or side effects for these novel compounds.…”