Effects of DA D1 and D2 agonists on reward sensitivity

Illinois State University, Normal IL

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Abstract

DESCRIPTION (provided by applicant): The goal of the proposed research is to investigate the role of dopamine (DA), and in particular DA D1 and D2 receptors, in choice behavior using a matching law model of choice. Traditionally, dopamine had been considered the neural substrate of reward. However, recent models relating dopamine to behavior have suggested a better description of dopamine may be as the neural substrate of arousal, novelty or surprise. Further, it appears dopaminergic D1- like and D2-like receptors may mediate different classes of behavior corresponding to changes in arousal, and that these different arousal topographies may differentially affect choice behavior. Previous investigations have focused on describing behavior resulting from stimulation of DA D1 or D2 receptors, including motoric or automated behavior changes, sniffing, grooming or chewing. However, few investigations have examined the relationship between dopaminergic arousal and choice. Thus, there remains a gap in research bridging the relationship between DA-elicited arousal and choice responding, particularly investigations relating changes in the response topography with changes sensitivity to reward. The proposed project examines how changes in arousal produced by DA D1 and D2 agonists may affect response topography, which in turn may affect operant responding. Changes in sensitivity will be examined using a matching law paradigm in conjunction with video analysis of changes in the topography of operant and adjunctive behavior as arousal levels are altered. The project attempts to determine if animals decrease all responding or simply alter their pattern of responding when exposed to DA D1-like and D2-like receptor agonists. Three experiments are outlined examining: 1) changes in sensitivity to reinforcement when animals are exposed to a series of doses of partial and full D1 agonist, SKF38393 and SKF82958 respectively; a D2 agonist quinpirole, a D3 selective agonist PD 128,907 used to control for D3 receptor effects, and a non-selective DA agonist, apomorphine; 2) how the value of the available operant reward and the value of adjunctive behaviors changes when animals are exposed to these agonists; and 3) how exposure to these agonists may affect within-session contrast and induction.