Jang Han Byeol, Ahn DanBi, Kim Hyung Kyu, Guan Xiaowei, Fan Yu, Lee Bae Hwan, Kim Hee Young
Department of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea.
Front Mol Neurosci. 2023 Jul 12;16:1195939. doi: 10.3389/fnmol.2023.1195939. eCollection 2023.
The lateral hypothalamus (LH) plays an important physiological role in brain function and also plays an important role in substance abuse. The neuropeptides called orexin (or hypocretins) have been identified as being located exclusively in the cell bodies of the LH. Our previous studies have demonstrated that mechanical stimulation (MS) of the ulnar nerve produces strong inhibitory effects on cocaine addiction-like behaviors through activation of LH projection to the lateral habenula (LHb).
Therefore, the present study hypothesized that ulnar MS would suppress the psychomotor responses induced by cocaine through the orexinergic LH-to-LHb pathway.
Ulnar MS attenuated cocaine enhancement of locomotor activity and 50-kHz ultrasonic vocalizations, which was prevented by antagonism of orexin-receptor type 2 (OX2R) in the LHb. Injection of orexin-A into the LHb reduced the cocaine-induced psychomotor responses. MS of the ulnar nerve excited LH orexinergic neurons. In addition, the excitation of LHb neurons by MS was blocked by the systemic administration of an OX2R antagonist.
These findings suggest that MS applied to the ulnar nerve recruits an orexinergic LH-to-LHb pathway to suppress the psychomotor responses induced by cocaine.
外侧下丘脑（LH）在脑功能中发挥重要生理作用，在药物滥用方面也起着重要作用。被称为食欲素（或下丘脑泌素）的神经肽已被确定仅位于LH的细胞体中。我们之前的研究表明，尺神经的机械刺激（MS）通过激活LH向外侧缰核（LHb）的投射，对可卡因成瘾样行为产生强烈抑制作用。
因此，本研究假设尺神经MS会通过食欲素能的LH至LHb通路抑制可卡因诱导的精神运动反应。
尺神经MS减弱了可卡因对运动活动和50 kHz超声发声的增强作用，而LHb中2型食欲素受体（OX2R）的拮抗作用可阻止这种减弱。向LHb注射食欲素-A可降低可卡因诱导的精神运动反应。尺神经MS使LH食欲素能神经元兴奋。此外，全身性给予OX2R拮抗剂可阻断MS对LHb神经元的兴奋作用。
这些发现表明，施加于尺神经的MS会激活一条从LH到LHb的食欲素能通路，以抑制可卡因诱导的精神运动反应。
