title: Rapid, reversible activation of AgRP  neurons drives feeding behavior in mice.
abstract: Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the evidence supporting this view is incomplete. Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, we have demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores. All these effects returned to baseline after stimulation was withdrawn. In contrast, inhibiting AgRP neuronal activity in hungry mice reduced food intake. Together, these findings demonstrate that AgRP neuron activity is both necessary and sufficient for feeding. Of interest, activating AgRP neurons potently increased motivation for feeding and also drove intense food-seeking behavior, demonstrating that AgRP neurons engage brain sites controlling multiple levels of feeding behavior. Due to its ease of use and suitability for both acute and chronic regulation, DREADD technology is ideally suited for investigating the neural circuits hypothesized to regulate energy balance.
authors.affiliation: Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Krashes
authors.forename: Shuichi
authors.initials: S
authors.lastname: Koda
authors.forename: ChianPing
authors.initials: C
authors.lastname: Ye
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Rogan
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Adams
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Cusher
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Maratos-Flier
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D003024:Clozapine; C079149:clozapine N-oxide