Abstract:

Objective: To explore the role of oxytocin receptor (OTR) in regulating anxiety- and depression-like behaviors and monoamine, amino acids and choline neurotransmitters in the cerebral cortex. And to investigate the effects of osthole on neurotransmitters in OTR silencing rats.Method: OTR silencing rats were established via short hairpin RNA (shRNA). Elevated plus maze and forced swimming test were used to observe the effect of osthole on anxiety- and depression-like behaviors. Q-orbitrap HPLC-HRMS was applied to detect neurotransmitters in the cerebral cortex of rats.Results: In the elevated plus maze, the number of entering the open arms and the residence time in the open arms were significantly reduced in the OTR-shRNA rats compared with the control group (P<0.05). Osthole (12.5 mg·kg^-1) treatment increased the number of entering the open arms and the residence time in the open arms compared with the OTR-shRNA group (P<0.01). Forced swimming test showed that the OTR-shRNA group rats were immobile for longer than the control group (P<0.05). The immobile time in the osthole (12.5 mg·kg^-1and 25 mg·kg^-1) groups were reduced than that in the OTR-shRNA group (P<0.05). Compared with the control group, the levels of dopamine (DA) and L-glutamic acid in the cerebral cortex of the OTR-shRNA group were higher (P<0.05), and the levels of 5-hydroxytryptamine (5-HT), gamma aminobutyric acid (GABA), and acetylcholine (Ach) were significantly lower (P<0.05). Osthole (12.5 mg·kg^-1) reduced the level of DA, and increased the level of 5-HT, GABA and Ach (P<0.05), whereas osthole (25 mg·kg^-1) increased the level of 5-HT and Ach (P<0.05).Conclusions:Osthole could influence neurotransmitters in the cerebral cortex, and attenuate anxiety- and depression-like behaviors, which may be through regulating the OTR pathway. It provides a new direction and basis for the research in central nervous system disorders, such as depression.

Key words:anxiety and depression,gene silencing,oxytocin receptor,neurotransmitters,osthole