Gradev Albert R, Rashev Pavel I, Atanasova Dimitrinka Y, Dandov Angel D, Lazarov Nikolai E
Department of Anatomy and Histology, Medical University of Sofia, 1431 Sofia, Bulgaria.
Institute of Biology and Immunology of Reproduction "Acad. Kiril Bratanov", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Int J Mol Sci. 2025 Aug 18;26(16):7955. doi: 10.3390/ijms26167955.
The bed nucleus of the stria terminalis (BNST) is a heterogeneous and complex limbic forebrain structure, which plays an important role in drug addiction and anxiety. Dynorphin and kappa-opioid receptors (DYN/KOR) comprise a crucial neural system involved in modulating stress-induced drug and alcohol addiction. Previous studies have highlighted the BNST as a brain region with a strong DYN/KOR expression. However, no research has been conducted on the adolescent plasticity of this system. In the present study, we used 20- and 60-day-old Wistar rats to reveal the adolescent dynamics and possible sex differences of the DYN/KOR system in certain BNST nuclei associated with addiction behavior. We found a low expression of DYN in neuronal perikarya and a significant increase in DYN-containing nerve fibers in the lateral posterior and lateral dorsal nuclei of the rat BNST. In addition, an enhanced expression of KORs was observed in the examined BNST subnuclei with some sex differences favoring females, thus highlighting the importance of considering critical developmental differences between sexes in research. The dynamics of the DYN/KOR system observed in this study may help to explain the increased vulnerability of adolescents for developing drug and alcohol addiction.
终纹床核（BNST）是一个异质性且复杂的边缘前脑结构，在药物成瘾和焦虑中发挥重要作用。强啡肽和κ-阿片受体（DYN/KOR）构成了一个关键的神经系统，参与调节应激诱导的药物和酒精成瘾。先前的研究强调BNST是一个具有强DYN/KOR表达的脑区。然而，尚未对该系统的青春期可塑性进行研究。在本研究中，我们使用20日龄和60日龄的Wistar大鼠，以揭示与成瘾行为相关的特定BNST核中DYN/KOR系统的青春期动态变化及可能存在的性别差异。我们发现大鼠BNST的外侧后核和外侧背核中神经元胞体的DYN表达较低，而含DYN的神经纤维显著增加。此外，在所检测的BNST亚核中观察到KORs表达增强，且存在一些有利于雌性的性别差异，从而突出了在研究中考虑两性关键发育差异的重要性。本研究中观察到的DYN/KOR系统动态变化可能有助于解释青少年药物和酒精成瘾易感性增加的现象。
