Open AccessDopamine D2 receptor overexpression in the nucleus accumbens core induces robust weight loss during scheduled fasting selectively in female mice
Author(s) -
Alexander Welch,
Jie Zhang,
Jinrui Lyu,
Matthew S. McMurray,
Jonathan Javitch,
Christoph Kellendonk,
Stephanie C. Dulawa
Publication year - 2019
Publication title -
molecular psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.071
H-Index - 213
eISSN - 1476-5578
pISSN - 1359-4184
DOI - 10.1038/s41380-019-0633-8
Subject(s) - hypophagia , nucleus accumbens , endocrinology , medicine , dopamine receptor d2 , open field , dopamine , weight loss , striatum , body weight , biology , obesity
Anorexia nervosa (AN) is an eating disorder observed predominantly in women and girls that is characterized by a low body-mass index, hypophagia, and hyperactivity. Activity-based anorexia (ABA), which refers to the weight loss, hypophagia, and hyperactivity exhibited by rodents exposed to both running wheels and scheduled fasting, provides a model for aspects of AN. Increased dopamine D2/D3 receptor binding in the anteroventral striatum has been reported in AN patients. We virally overexpressed D2Rs on nucleus accumbens core (D2R-OE NAc ) neurons that endogenously express D2Rs, and tested mice of both sexes in the open field test, ABA paradigm, and intraperitoneal glucose tolerance test (IGTT). D2R-OE NAc did not alter baseline body weight, but increased locomotor activity in the open field across both sexes. During constant access to food and running wheels, D2R-OE NAc mice of both sexes increased food intake and ran more than controls. However, when food was available only 7 h a day, only female D2R-OE NAc mice rapidly lost 25% of their initial body weight, reduced food intake, and substantially increased wheel running. Surprisingly, female D2R-OE NAc mice also rapidly lost 25% of their initial body weight during scheduled fasting without wheel access and showed no changes in food intake. In contrast, male D2R-OE NAc mice maintained body weight during scheduled fasting. D2R-OE NAc mice of both sexes also showed glucose intolerance in the IGTT. In conclusion, D2R-OE NAc alters glucose metabolism in both sexes but drives robust weight loss only in females during scheduled fasting, implicating metabolic mechanisms in this sexually dimorphic effect.