Dissociative effects of dorsomedial striatum D1 and D2 receptor antagonism in the regulation of anxiety and learned approach-avoidance conflict decision-making

Abstract

ABSTRACT The dorsal striatum is traditionally known for its role in sensorimotor integration. However, the dorsomedial striatum (DMS) has also been implicated in cost‐benefit conflict processing, a role more readily attributed to the ventral striatum (VS), as a site of limbic‐motor integration. We recently showed that dopaminergic D1 (D1R) and D2 receptors (D2R) in the VS exert dissociable control over cue‐elicited approach‐avoidance decision‐making, in the presence of conflicting motivational stimuli. We therefore sought to investigate the contribution of DMS dopaminergic receptors in the regulation of cue‐elicited and innate approach‐avoidance decision‐making. Using a conditioned mixed‐valence conflict paradigm, we trained rats in a three‐arm radial maze to associate visuotactile cues with appetitive, aversive, and neutral outcomes. Rats then received an intra‐DMS or intra‐dorsolateral striatum (DLS) microinfusion of D1‐like antagonist (SCH23390) or D2‐like antagonist (sulpiride), and were then tested for the expression of approach‐avoidance behavior in a conflict scenario, wherein the appetitive and aversive cues were superimposed within a single maze arm. The results revealed that DMS (but not DLS) D1R antagonism, suppressed approach towards the conflict arm while DMS (but not DLS) D2R antagonism enhanced approach. All rats were subsequently administered an elevated plus maze test as a measure of innate approach‐avoidance conflict (anxiety). DMS D1R antagonism decreased anxiety, while DMS D2R and both DLS D1R and D2R antagonism increased anxiety. Our findings suggest that under motivational conflict, activation of DMS D1‐like receptors facilitates approach, while activation of D2‐like receptors suppress approach behavior. Furthermore, anxiety is regulated by dorsal striatal‐mediated dopaminergic mechanisms. HIGHLIGHTSDorsomedial striatum D1R blockade induced avoidance of motivational conflict cues.Dorsomedial striatum D2R blockade induced enhanced approach of conflict cues.Dorsomedial striatum D1R blockade caused anxiolysis in elevated plus maze.Dorsomedial striatum D2R blockade caused anxiogenesis in elevated plus maze.Dorsolateral striatal D1R/D2R receptor blockade increased anxiety.