D2-dopamine receptors and the development of obesity

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIDDK	NEURO-7

Authors

• D.M. Friend
• K. Devarakonda
• J.C. Lemos
• A Kaplan
• V.A. Alvarez
• A.V. Kravitz

Abstract

Striatal D2 dopamine receptor (D2R) availability and weight are negatively correlated, where obese individuals have decreased striatal D2R availability compared to lean counterparts. Furthermore, striatal D2R-expressing neurons regulate movement and motivated behaviors, suggesting that alterations in D2R play an important role in obesity-related symptoms. However, it remains unclear how decreased D2R availability leads to behaviors associated with obesity or how the function of D2R-expressing neurons changes when expression of the D2R is reduced. To explore this, we used a conditional transgenic mouse model where the D2R is selectively eliminated from the major population of striatal neurons that express it (Drd2-KO mice). We found that Drd2-KO mice have decreased movement compared to wildtype mice. Additionally, when given the opportunity to use running wheels, Drd2-KO mice spend significantly less time running than wiltype mice. Next, we examined whether decreased D2R expression results in alterations in striatal neuron firing in vivo. Average striatal firing rates were significantly lower in Drd2-KO mice compared to wildtype mice. These results indicate that reductions in striatal D2R play an important role in movement, which may promote future weight gain. We are currently examining whether Drd2-KO animals gain more weight than wildtype mice when fed high-fat diet.

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