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

Jocelyn M. Richard, Kent C. Berridge

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish (US)
Pages (from-to)12866-12879
Number of pages14
JournalJournal of Neuroscience
Issue number36
StatePublished - Sep 7 2011
Externally publishedYes

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