Striatal GPR88 Modulates Foraging Efficiency

The striatum is anatomically and behaviorally implicated in behaviors that promote efficient foraging. To investigate this function, we studied instrumental choice behavior in mice lacking GPR88, a striatum-enriched orphan G-protein-coupled receptor that modulates striatal medium spiny neuron excitability. Our results reveal that hungry mice lacking GPR88 (KO mice) were slow to acquire food-reinforced lever press but could lever press similar to controls on a progressive ratio schedule. Both WT and KO mice discriminated between reward and no-reward levers; however, KO mice failed to discriminate based on relative quantity-reward (1 vs 3 food pellets) or effort (3 vs 9 lever presses). We also demonstrate preference for the high-reward (3 pellet) lever was selectively reestablished when GPR88 expression was restored to the striatum. We propose that GPR88 expression within the striatum is integral to efficient action-selection during foraging. SIGNIFICANCE STATEMENT Evolutionary pressure driving energy homeostasis favored detection and comparison of caloric value. In wild and laboratory settings, neural systems involved in energy homeostasis bias foraging to maximize energy efficiency. This is observed when foraging behaviors are guided by superior nutritional density or minimized caloric expenditure. The striatum is anatomically and functionally well placed to perform the sensory and motor integration necessary for efficient action selection during foraging. However, few studies have examined this behavioral phenomenon or elucidated underlying molecular mechanisms. Both humans and mice with nonfunctional GPR88 have been shown to present striatal dysfunctions and impaired learning. We demonstrate that GPR88 expression is necessary to efficiently integrate effort and energy density information guiding instrumental choice.