title: Nucleus accumbens dopamine/glutamate interaction switches modes to generate desire versus dread: D(1) alone for appetitive eating but D(1) and D(2) together for fear.
abstract: 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 by AMPA disruptions. Here we report that only endogenous local signaling at D(1) 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 D(1) and D(2) 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 D(1) and D(2) signaling in dopamine/glutamate interaction at microinjection sites also switched dynamically to match the motivation valence generated at the moment. Thus, NAc D(1) and D(2) 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.
authors: Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109-1043, USA. jocelyri@umich.edu
authors: Jocelyn M
authors: JM
authors: Richard
authors: Kent C
authors: KC
authors: Berridge
mesh_terms: D000818:Animals; D001066:Appetite / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004435:Eating / Q000502:physiology*; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000502:physiology*; D016762:Genes, fos; D005917:Globus Pallidus / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000502:physiology; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000502:physiology
chemical_list: D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018698:Glutamic Acid; C056723:FG 9041; D004298:Dopamine