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- Title
Rapid, reversible activation of AgRP neurons drives feeding behavior in mice.
- Authors
Krashes, Michael J.; Shuichi Koda; ChianPing Ye; Rogan, Sarah C.; Adams, Andrew C.; Cusher, Daniel S.; Maratos-Flier, Eleftheria; Roth, Bryan L.; Lowell, Bradford B.; Koda, Shuichi; Ye, ChianPing
- 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 All these effects returned to baseline after stimulation was withdrawn.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.
- Subjects
NEURON development; ANIMAL feeding behavior; PHYSIOLOGICAL control systems; HOMEOSTASIS; NEURAL circuitry; LABORATORY mice; BRAIN physiology; HYPOTHALAMUS physiology; NEURAL physiology; ANIMAL experimentation; BRAIN; CLOZAPINE; ENERGY metabolism; FOOD habits; GROWTH factors; HYPOTHALAMUS; INGESTION; MICE; NEURONS; RESEARCH funding; WEIGHT gain; PHARMACODYNAMICS
- Publication
Journal of Clinical Investigation, 2011, Vol 121, Issue 4, p1424
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI46229