Effects of manipulating prefrontal activity and dopamine D1 receptor signaling in an appetitive feature-negative discrimination learning task

Healthy cognition requires inhibitory modulation of associative learning; conversely, impaired inhibitory discrimination is implicated in behavioral disorders. The medial prefrontal cortex (mPFC) and its dopamine innervation are key to understanding inhibition and impulsivity. We therefore examined the role of prelimbic and infralimbic cortices in within-subjects appetitive feature-negative learning using microinfusions of (a) the gamma-aminobutyric acid-A receptor agonist muscimol (0.25 μg in 1.0 μl; = 35), (b) the dopamine D1 receptor agonist SKF-81297 (0.1 μg in 1.0 μl; = 33), and (c) the dopamine D1 receptor antagonist SCH-23390 (5 μg in 1.0 μl; = 35). A conditioned stimulus (CS) was followed by food, but on trials on which the CS (A+) was compounded with the inhibitory cue (AX-), the food delivery was canceled. Difference scores (CS-preCS responding) were used to measure learning. All three experiments showed the feature-negative discrimination (A+/AX-), as decreased responding to AX- versus A+. This discrimination was reduced but preserved following muscimol infusions in Experiment 1. Similarly, in Experiments 2 and 3, infusions of SKF-81297 and SCH-23390 were both without effect on the acquisition of the discrimination. Like muscimol, SCH-23390 reduced difference score responding, consistent with nonspecific effects on the (expression of) learning. Thus, there was no evidence to suggest that inactivation of prelimbic or infralimbic cortices impaired feature-negative discrimination learning and no evidence for dopaminergic modulation of such learning in the medial prefrontal cortex either. These results are discussed in the context of the nonspecific effects of the infusions and the overall inconsistent performance in summation and retardation tests of conditioned inhibition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).