Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
Michael J. Krashes, … , Bryan L. Roth, Bradford B. Lowell
Michael J. Krashes, … , Bryan L. Roth, Bradford B. Lowell
Published March 1, 2011
Citation Information: J Clin Invest. 2011;121(4):1424-1428. https://doi.org/10.1172/JCI46229.
View: Text | PDF
Brief Report Neuroscience

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 All these effects returned to baseline after stimulation was withdrawn.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

Michael J. Krashes, Shuichi Koda, ChianPing Ye, Sarah C. Rogan, Andrew C. Adams, Daniel S. Cusher, Eleftheria Maratos-Flier, Bryan L. Roth, Bradford B. Lowell

×

Figure 3

Stimulating AgRP neurons drives a behavioral program to work for and search for food.

Options: View larger image (or click on image) Download as PowerPoint
Stimulating AgRP neurons drives a behavioral program to work for and sea...
(A) Ad lib–fed animals injected with saline were first trained to associate a successful nose poke with a reward pellet using an FR1 schedule. Following the training period, the same cohort was injected with CNO (0.3 mg/kg of body weight, i.p.) or saline and then tested on a PR3. Acute stimulation of AgRP neurons in mice fed ad lib led to a significant increase in the break point, similar to the break point observed in fasted mice. Data shown are from male mice (mean ± SEM, n = 6, *P < 0.01). (B) Stimulation of AgRP neurons increases physical activity when food is absent but not when food is present. In the food-absent study, food was removed immediately following CNO or saline injection. The number of ambulatory episodes along the horizontal plane was assessed 0–1 hour, 1–2 hours, 2–3 hours, 3–4 hours, and 4–5 hours PI. The same cohort of mice was used in the food – and food + studies. Data shown are from male mice (mean ± SEM, n = 4, *P < 0.01).