腹侧被盖区强啡肽调控抑郁相关绝望行为的受体机制研究

Dynorphin in the ventral tegmental area mediates depressive-likedespaired behavior by targeting the к opioid receptor

目的探究腹侧被盖区(ventral tegmental area,VTA)微量注射外源性强啡肽对小鼠抑郁相关绝望行为的调控作用及其受体机制。方法通过脑立体定位技术将特制的注药套管置入小鼠VTA并微量注射κ受体特异性激动剂强啡肽100 pmol或特异性拮抗剂nor-BNI(nor-Binaltorphimine)200 pmol,通过形态学方法验证置管位置,借助悬尾实验(tail suspension test,TST)和强迫游泳实验(forced swimming test,FST)衡量小鼠的抑郁相关绝望行为。结果通过套管给予外源性к受体特异性激动剂强啡肽明显延长小鼠在悬尾实验和强迫游泳实验中的不动时间,这种效应可以被预先注射к受体特异性拮抗剂nor-BNI完全拮抗。结论强啡肽可能通过激活VTA内к受体诱发小鼠抑郁相关的绝望行为,预先阻断VTA内к受体可以拮抗强啡肽的致抑郁样作用。

Objective To investigate the effects of exogenous dynorphin injection in ventral tegmental area(VTA)on depression-related despairing behavior of mice and related mechanisms.Methods A special cannula was implanted into VTA through cerebral stereotaxic technique and 100 pmol dynorphin(кreceptor specific agonist)or 200 pmol nor-BNI(nor-Binaltorphimine,a specific antagonist)was injected.The position of the canula was morphologically verified.The tail suspension test(TST)and forced swimming test(FST)were used to evaluate desperation-related despairing behavior in mice.Results Exogenous administration of dynorphin via the cannula remarkably extend the immovable time of mice in TST and FST,which could be completely inhibited through pre-injection of nor-BNI.Conclusions Dynorphin may induce depression-related despairing behaviors through activatingкreceptors in VTA,which is blocked by pre-inhibition ofкreceptor in VTA.