Amygdalar Regulation of Nucleus Accumbens Reward Signaling

DESCRIPTION (provided by applicant): Organisms direct actions towards specific goals and rewards, whether they are natural or drug rewards. It is essential for survival that actions result in successful pursuit of natural rewards, and often in the human condition, this pursuit can be usurped and directed towards unnatural rewards, such as drugs of abuse. Often these actions are guided by environmental cues and associations that may direct or influence the behavioral directions taken. These goal-directed actions, and the environmental associations relevant to them, likely involve the concerted activation of specific brain regions and neurotransmitter systems. The nucleus accumbens (NAc), often referred to as a limbic-motor interface, and its dopaminergic inputs are intimately involved in the modulation of food and drug reinforcement, specifically in the encoding of goal- directed action during self-administration. Furthermore, the amygdala, a related limbic structure, has been implicated in the formed association between environmental cues and predicted rewards. Together these structures likely form an integrated circuit regulating stimulus-reward associations. This proposal seeks to examine cellular and neurochemical activity in the NAc during a self-administration task, while simultaneously manipulating the amygdala and its NAc efferents. Multi-cellular electrophysiology and fast- scan cyclic voltammetry will be used to examine nucleus accumbens cell firing and subsecond dopamine release, respectively, during a self-administration paradigm. Functional manipulation of the amygdala will be accomplished using pharmacological microinjections. Taken together, the results of this study will provide insight into the functional circuitry involved in the neural encoding of goal-directed behaviors and the environmental cues associated with them. Relevance to Public Health: One of the most debilitating aspects of drug addiction is the susceptibility to relapse (resumption of drug taking after long periods of abstaining), often triggered by the environment or situation associated with previous drug taking. In the effort to understand addictive behaviors, we must first understand the underlying biological mechanisms of how things around us become associated with the rewards we take. This proposal seeks to describe the circuitry of these mechanisms, and in so doing provide key information for the development of pharmacological treatments for drug addiction in humans.