Disentangling the diverse roles of dopamine D2 receptors in striatal function and behavior

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Dopamine D2 receptors (D2Rs) mediate many of the actions of dopamine in the striatum, ranging from movement to the effortful pursuit of reward. Yet despite significant advances in linking D2Rs to striatal functions with pharmacological and genetic strategies in animals, how dopamine orchestrates its myriad actions on different cell populations —each expressing D2Rs— remains unclear. Furthermore, brain imaging and genetic studies in humans have consistently associated striatal D2R alterations with various neurological and neuropsychiatric disorders, but how and which D2Rs are involved in each case is poorly understood. Therefore, a critical first step is to engage in a refined and systematic investigation of the impact of D2R function on specific striatal cells, circuits, and behaviors. Here, I will review recent efforts, primarily in animal models, aimed at unlocking the complex and heterogeneous roles of D2Rs in striatum.HIGHLIGHTSDopamine D2 receptors mediate many of the functions of dopamine in striatum.Various disorders feature alterations in striatal D2 receptors.Their precise role in shaping circuits and behavior are not well understood.Recent studies have begun to dissect their roles in health and disease.

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