Nutrient-dependent hippocampus dopamine signaling enhances meal-related episodic memory and reduces food intake

Background: Dopamine (DA) is a neurotransmitter critically involved in food-related reinforcement learning. While mesolimbic DA reward-associated signaling in the nucleus accumbens has been widely investigated, far less is known about DA function in the hippocampus (HPC), a brain region traditionally known for its role in episodic and spatial memory processes that has recently been associated with appetite and food intake control. Methods: Here we investigated dorsal HPC DA signaling dynamics in rats using fiber photometry to detect changes in DA binding (via GRAB-DA sensors) before, during, and after a meal consumption in food-restricted rats. Pharmacological studies targeting HPC dopamine 2 receptors (D2R) assessed the functional role of HPC DA signaling in food intake and meal-related memory processes. Results: HPC DA binding was significantly elevated in the post-meal relative to the pre-meal state following standard chow consumption. This effect was replicated after consuming a high fat diet or liquid sucrose, but not a low-calorie sweetener. These post-meal DA signaling elevations are dependent on nutrient consumption, as HPC DA binding levels were unaffected by intraperitoneal administration of glucose or the satiation hormone, cholecystokinin, in otherwise fasted rats. Direct HPC D2R agonists administration reduced food intake, whereas HPC D2R blockade after a meal reduced the latency to the next meal and impaired spatial memory for meal location without affecting spatial memory for object location. Conclusions: Collective results identify HPC DA-D2R signaling as a candidate neurobiological mechanism through which nutrient consumption promotes meal-related episodic memory formation, and by extension, reduces subsequent food intake.