TY - JOUR
T1 - A D2 to D1 shift in dopaminergic inputs to midbrain 5-HT neurons causes anorexia in mice
AU - Cai, Xing
AU - Liu, Hailan
AU - Feng, Bing
AU - Yu, Meng
AU - He, Yang
AU - Liu, Hesong
AU - Liang, Chen
AU - Yang, Yongjie
AU - Tu, Longlong
AU - Zhang, Nan
AU - Wang, Lina
AU - Yin, Na
AU - Han, Junying
AU - Yan, Zili
AU - Wang, Chunmei
AU - Xu, Pingwen
AU - Wu, Qi
AU - Tong, Qingchun
AU - He, Yanlin
AU - Xu, Yong
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/5
Y1 - 2022/5
N2 - Midbrain dopamine (DA) and serotonin (5-HT) neurons regulate motivated behaviors, including feeding, but less is known about how these circuits may interact. In this study, we found that DA neurons in the mouse ventral tegmental area bidirectionally regulate the activity of 5-HT neurons in the dorsal raphe nucleus (DRN), with weaker stimulation causing DRD2-dependent inhibition and overeating, while stronger stimulation causing DRD1-dependent activation and anorexia. Furthermore, in the activity-based anorexia (ABA) paradigm, which is a mouse model mimicking some clinical features of human anorexia nervosa (AN), we observed a DRD2 to DRD1 shift of DA neurotransmission on 5-HTDRN neurons, which causes constant activation of these neurons and contributes to AN-like behaviors. Finally, we found that systemic administration of a DRD1 antagonist can prevent anorexia and weight loss in ABA. Our results revealed regulation of feeding behavior by stimulation strength-dependent interactions between DA and 5-HT neurons, which may contribute to the pathophysiology of AN.
AB - Midbrain dopamine (DA) and serotonin (5-HT) neurons regulate motivated behaviors, including feeding, but less is known about how these circuits may interact. In this study, we found that DA neurons in the mouse ventral tegmental area bidirectionally regulate the activity of 5-HT neurons in the dorsal raphe nucleus (DRN), with weaker stimulation causing DRD2-dependent inhibition and overeating, while stronger stimulation causing DRD1-dependent activation and anorexia. Furthermore, in the activity-based anorexia (ABA) paradigm, which is a mouse model mimicking some clinical features of human anorexia nervosa (AN), we observed a DRD2 to DRD1 shift of DA neurotransmission on 5-HTDRN neurons, which causes constant activation of these neurons and contributes to AN-like behaviors. Finally, we found that systemic administration of a DRD1 antagonist can prevent anorexia and weight loss in ABA. Our results revealed regulation of feeding behavior by stimulation strength-dependent interactions between DA and 5-HT neurons, which may contribute to the pathophysiology of AN.
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U2 - 10.1038/s41593-022-01062-0
DO - 10.1038/s41593-022-01062-0
M3 - Article
C2 - 35501380
AN - SCOPUS:85129204427
SN - 1097-6256
VL - 25
SP - 646
EP - 658
JO - Nature neuroscience
JF - Nature neuroscience
IS - 5
ER -