Nucleus accumbens dopamine/glutamate interaction switches modes to generate desire versus dread: D₁ alone for appetitive eating but D₁ and D₂ together for fear

The medial shell of nucleus accumbens (NAc) and its mesolimbic dopamine inputs mediate forms of fearful as well as of incentive motivation. For example, either appetitive and/or actively fearful behaviors are generated in a keyboard pattern by localized glutamate disruptions in NAc (via microinjection of the AMPA receptor antagonist DNQX) at different anatomical locations along a rostrocaudal gradient within the medial shell of rats. Rostral glutamate disruptions produce intense increases in eating, but more caudally placed disruptions produce increasingly fearful behaviors: distress vocalizations and escape attempts to human touch, and a spontaneous and directed antipredator response called defensive treading/burying. Local endogenous dopamine is required for either intense motivation to be generated byAMPAdisruptions. Here we report that only endogenous local signaling atD₁ dopamine receptors is needed for rostral generation of excessive eating, potentially implicating a direct output pathway contribution. In contrast, fear generation at caudal sites requires both D₁ and D₂ signaling simultaneously, potentially implicating an indirect output pathway contribution. Finally, when motivation valence generated by AMPA disruptions at intermediate sites was flipped by manipulating environmental ambience, from mostly appetitive in a comfortable home environment to mostly fearful in a stressful environment, the roles of local D₁ and D₂ signaling in dopamine/glutamate interaction at microinjection sites also switched dynamically to match the motivation valence generated at the moment. Thus, NAc D₁ and D₂ receptors, and their associated neuronal circuits, play different and dynamic roles in enabling desire and dread to be generated by localized NAc glutamate disruptions in medial shell.