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Gene & Protein in Disease Orexin in depression

expression in specific neural circuits. GABA receptors are research, treatment, and prevention of mental diseases
A
located in the presynaptic terminals, and their activation such as depression through a comprehensive review of
151
allows Cl to flow into postsynaptic neurons and induce orexin and depression.
−
152
inhibitory postsynaptic potentials. In contrast, GABA
B
receptors are distributed at presynaptic and postsynaptic Acknowledgments
sites, and their functions typically involve the regulation None.
of neurotransmitter release and neuronal excitability,
with their role at the presynaptic site closely associated Funding
with spinal presynaptic inhibition caused by primary- This work was supported by the Key Scientific
afferent depolarization. Consequently, decreasing GABA Research Program for Universities of Henan Province
release may disturb the excitatory–inhibitory balance, (no. 22A320029), the Key Science and Technology
which is particularly evident in the interaction between Program of Henan Province in China (no. 242102310274),
glutamatergic and GABAergic neurons. 153,154 Orexin the Medical Science and Technology Program of
increases dopamine and regulates reward and motivational Henan Province (no. SBGJ202103096), the Program for
behavior through interactions with dopamine receptors. Innovative Talents of Science and Technology in Henan
In addition to its involvement in regulating mood and the Province (no. 23HASTIT043), and the Cultivation Project
sleep–wake cycle, orexin is implicated in various aspects for Innovation Team in Teachers’ Teaching Proficiency by
of stress response and substance abuse. For instance, Zhengzhou Shu-Qing Medical College (No. 2024jxcxtd01).
orexin interacts with the noradrenaline system and HPA
axis, regulating the HPA axis by increasing the release Conflict of interest
of norepinephrine (Figure 5) and modulating stress The authors declare no conflicts of interest.
responses and improving alertness. The hypothalamic-
ventral tegmental pathway is a crucial regulator of appetite Author contributions
and energy balance. Within this pathway, the activity of
orexin neurons substantially promotes feeding behavior. Conceptualization: Ying Wang, Xinying Ji, Shuangyu Lv
Animals that lack orexin experience a loss of appetite Visualization: Chen Dong, Ying Wang, Shuangyu Lv,
and subsequent weight loss. The hypothalamic-ventral Xinying Ji
thalamic pathway also considerably regulates reward Writing–original draft: Chen Dong
behavior and drug abuse. The activity of orexin neurons Writing–review & editing: Ying Wang, Xinying Ji, Shuangyu
can improve reward behaviors and participate in drug Lv, Yaping Sun, Jiawei Xu, Shuoshuo Guo
craving and abuse behaviors. Ethics approval and consent to participate
Nonetheless, the mechanism of action of orexin in Not applicable.
depression remains unclear, and a lack of such data is the
biggest obstacle to a comprehensive understanding of the Consent for publication
pathophysiology of depression. Further, exploring the
interactions between orexin and other neurotransmitters Not applicable.
and signaling pathways, as well as its specific role in Availability of data
the development of depression, is necessary. Moreover,
depressive symptoms can be improved by regulating Not applicable.
the orexin system, and orexin receptor antagonists have
demonstrated potential to treat depression. Therefore, Further Disclosure
developing more selective and efficient orexin receptor No.
antagonists is a crucial focus for future research.
Overall, although orexin has demonstrated promise References
in depression studies, understanding its role across 1. Baimel C, Bartlett SE, Chiou LC, et al. Orexin/hypocretin
depression subtypes remains challenging. Future research role in reward: Implications for opioid and other addictions.
should focus on clarifying the distinct effects of orexin Br J Pharmacol. 2015;172(2):334-348.
in atypical and melancholic depression, as well as its doi: 10.1111/bph.12639
association with comorbid conditions such as anxiety, 2. Thompson MD, Sakurai T, Rainero I, Maj MC,
which may present different responses to orexin-targeted Kukkonen JP. Orexin receptor multimerization versus
treatments. This article provides some suggestions for the functional interactions: Neuropharmacological implications

Volume 4 Issue 2 (2025) 16 doi: 10.36922/gpd.4210