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

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 (к receptor 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 activating к receptors in VTA, which is blocked by pre-inhibition of к receptor in VTA.