Jieting Kong - Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China
Shengli Gao - Department of Special Medicine, School of Basic Medicine, Qingdao University, Qingdao, China
Xiaoman He - Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China
Nana Zhang - Department of Clinical Laboratory, the Affiliated Hospital of Qingdao University, Qingdao, China
Jinfang Huang - Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China
Pengfei Ji - Qingdao Medical College, Qingdao University, Qingdao, China
Shouheng Yao - Qingdao Medical College, Qingdao University, Qingdao, China
Xiang Ren - Qingdao Medical College, Qingdao University, Qingdao, China
Yiru Wang - Qingdao Medical College, Qingdao University, Qingdao, China
Yanling Gong - Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Feifei Guo - Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao, China

Objective(s): To investigate the regulatory effects of the nucleus accumbens (NAcSh)-lateral hypothalamus (LHA) GABAergic neural pathway on palatable food (PF) intake via orexin-A expression in diet-induced obesity (DIO) rats. Materials and Methods: NAcSh-LHA GABAergic pathways were observed by fluorogold retrograde tracing combined with fluorescence immunohistochemistry, and the regulatory effects of this neural pathway on PF intake were detected after ۱) microinjection of GABA-A receptor agonist muscimol (MUS) or antagonist bicuculine (BIC) into LHA, ۲) electrical stimulation NAcSh, and ۳) blocking the orexin-A receptor by icv SB۳۳۴۸۶۷. Results: Compared with rats on a normal diet (ND), NAcSh-LHA GABAergic neurons in the DIO rats were significantly decreased, and orexin-A expression in LHA significantly increased (p <۰.۰۵). Microinjection of MUS into LHA significantly decreased the PF intake in both ND and DIO rats (p <۰.۰۵), and BIC could markedly increase the PF intake in the ND rats (p <۰.۰۵), but not the DIO rats (P>۰.۰۵). After NAcSh electrical stimulation or SB۳۳۴۸۶۷ ICV injection, the PF intake was significantly decreased in the DIO rats (p <۰.۰۵), and there was no significant difference after preadministration of BIC into LHA (P>۰.۰۵). Conclusion: This GABAergic pathway could regulate the expression of orexin-A in LHA and PF intake. Orexin-A neurons in LHA of DIO rats might be less sensitive to GABAergic signals and may consequently lead to more hedonic food intake.

Food intake, GABA, Nucleus accumbens, Obesity, Orexin-A