Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice

• Published in: Nature communications 2023-01, Vol.14 (1), p.71-16, Article 71
• Main Authors: Sheng, Huan, Lei, Chao, Yuan, Yu, Fu, Yali, Cui, Dongyang, Yang, Li, Shao, Da, Cao, Zixuan, Yang, Hao, Guo, Xinli, Chu, Chenshan, Wen, Yaxian, Cai, Zhangyin, Chen, Ming, Lai, Bin, Zheng, Ping
• Format: Article
• Language: English
• Subjects: 13/51; 14/32; 38/77; 631/378/1595; 631/378/1595/1395; 631/378/3920; 64/110; 64/60; 9/74; 96/1; 96/63; Addictions; Animals; Circuits; Context; Dopamine; Dopamine D1 receptors; Drug addiction; Drug withdrawal; Glutamatergic transmission; Humanities and Social Sciences; Hypothalamic Area, Lateral - metabolism; Hypothalamus; Hypothalamus (lateral); Luteinizing hormone; Male; Males; Mice; Morphine; Morphine - adverse effects; multidisciplinary; Neural networks; Neurons; Neurons - metabolism; Nucleus accumbens; Nucleus Accumbens - metabolism; Receptors, Dopamine D1 - metabolism; Science; Science (multidisciplinary); Spiny neurons; Substance-Related Disorders - metabolism; Withdrawal; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35758-5

The lateral hypothalamus (LH) is physiologically critical in brain functions. The LH also plays an important role in drug addiction. However, neural circuits underlying LH involvement of drug addiction remain obscure. In the present study,our results showed that in male mice, during context-induced expression of morphine withdrawal memory, LH glutamatergic neurons played an important role; dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) projecting from the core of nucleus accumbens (NAcC) to the LH were an important upstream circuit to activate LH glutamatergic neurons; D1-MSNs projecting from the NAcC to the LH activated LH glutamatergic neurons through inhibiting LH local gamma-aminobutyric acid (GABA) neurons. These results suggest that disinhibited LH glutamatergic neurons by neural circuits from the NAcC importantly contribute to context-induced the expression of morphine withdrawal memory. Lateral hypothalamus (LH) plays an role in drug addiction. Here, authors present evidence for disinhibited LH glutamatergic neurons by neural circuits from nucleus accumbens to contribute to context-induced expression of morphine withdrawal memory.