Taste disturbances are reported by patients with an array of psychopathologies in which dopamine is implicated, suggesting that certain taste functions may be dependent on dopaminergic signaling. Prior reports and the preliminary data presented in this proposal show that dopamine receptor antagonists that cross the blood-brain barrier reduce sucrose intake by rats by decreasing its palatability. However, although taste signals have hedonic valence that is related to their ability to unconditionally promote or discourage intake of fluids, they also 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. Preliminary findings provide evidence that peripheral injection of raclopride, a D2 receptor antagonist, actually 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 D2 receptor antagonism directly and/or indirectly decreases sucrose taste sensitivity at a basic sensory level in a rat model. The presence of the D2 receptor in hindbrain regions associated with taste, along with the preliminary data presented showing that 4th ventricular infusion of raclopride decreases sucrose intake, provides a likely site at which dopamine may be exerting its effects on taste-guided behavior. Thus the proposed experiments will assess the necessity of dopamine D2 receptor activation in the hindbrain on behaviors facilitated by the sensory and affective aspects of taste. I will also assess the extent to which dopamine impinges on sensory taste function by exploring the chemospecificity of the effects. The research proposed in this R03 application, which stem from my collective training in both the behavioral pharmacology of ingestive behavior and animal taste psychophysics, will begin to unravel the neurochemistry involved in normal and disordered taste-guided behavior starting with an assessment of dopamine. These experiments may help characterize not only basic taste function, but how it is disrupted in dopamine-related psychopathology, as well as help identify potential targets for pharmacological interventions aimed at curbing excessive food intake. The outcomes of these studies will serve as the basis for a subsequent R01 proposal in which the site-specificity of D2 antagonism on taste function could be further examined by selective parenchymal infusions. Ultimately, these experiments will guide the study of other neurochemical systems involved in normal and disordered taste function.
A subset of patients suffering from various psychopathologies in which dopamine is implicated report various disturbances in taste perception, and it is uncontested that dopamine influences motivated behavior, including food and fluid intake, which is, at least in part, guided by taste. Based on preliminary data presented in the research plan, I propose in this R03 to test the hypotheses that D2 receptors in the hindbrain are necessary for the normal expression of both reward-related and sensory-based taste-guided behaviors. The outcomes of these experiments may help characterize not only basic taste function, but how it is disrupted in dopamine- related psychopathology, as well as help identify potential targets for pharmacological interventions aimed at curbing excessive food intake.
