Central Dopaminergic Modulation of Sensory and Reward Taste Function in Rats.

Baldwin Wallace University, Berea OH

Investigators

Abstract

DESCRIPTION (provided by applicant): The sense of taste guides much of eating and drinking behavior. Nutritional status and quality of life are often negatively impacted when taste perception is altered, but the neurochemistry and circuitry mediating these taste changes remains to be determined. The contribution of dopamine to motivated and reward-driven behavior, including eating and drinking, is uncontested, and taste disturbances are reported by patients with an array of psychopathologies in which dopamine is implicated. Studies concerning the role of dopamine in taste- guided behavior have focused primarily on circuits in the forebrain, but dopaminergic machinery is also located in the hindbrain where peripheral taste nerves afferent. Prior reports have demonstrated that systemic administration of dopamine D2 receptor antagonists that cross the blood-brain barrier reduce hedonically driven sucrose intake by rats, and the preliminary data presented in this R03 proposal show that this is recapitulated when raclopride, a D2 receptor antagonist, is infused 4th intracerebroventricularly (4icv), a technique that broadly, but exclusively, targets hindbrain areas. However, although taste signals have hedonic valence that is related to their ability to unconditionally promote or discourage intake of fluids, they must first be detected. Thus, it is premature to conclude that dopaminergic modulation impacts only taste reward since a decrease in the strength of the perceived sensory taste signal may also result in decreased affective potency. Further preliminary findings presented here provide evidence that 4icv raclopride infusion decreases the detectability of sucrose by rats as assessed in an operant conditioning-based signal detection task using a specialized gustometer. These data suggest that hindbrain D2 receptor antagonism directly and/or indirectly decreases sucrose taste sensitivity at a basic sensory level in a rat model. The goal of the experiments proposed in this R03 application is to expand upon these promising preliminary data and evaluate the functional necessity of dopamine D2 receptors in the hindbrain using behavioral tasks that specifically address the sensory and affective aspects of taste. Specifically, the experiments will assess how the hedonically driven intake outcomes induced by 4icv raclopride infusion are behaviorally achieved and the extent to which D2 receptor blockade impinges on sensory taste function by exploring the chemo specificity of the effects. The outcomes of these functional studies, as well as an initial immunohistochemical assessment, will guide further mechanistic experiments, including those using selective parenchymal infusions that target specific brain areas. These future studies will serve as the foundation for an R01 proposal in which further multidisciplinary approaches can be used. Overall, the research proposed in this R03 application will begin to unravel the neurochemistry involved in normal and disordered taste-guided behavior starting with dopamine.