Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

International Journal of Molecular Sciences

Alexander Majouga¹  Kristina Soloveva²  Timur Syunyakov²  Vladimir Chekhonin³  Eugene Zubkov³  Anna Morozova³  Artemiy Silantyev³  Yana Zorkina³  Olga Abramova³  Valeria Ushakova³  Olga Gurina³ 

[1] Drug Delivery Systems Laboratory, D. Mendeleev University of Chemical Technology of Russia, Miusskaya pl. 9, 125047 Moscow, Russia;Mental-Health Clinic No. 1 Named after N.A. Alekseev, 117152 Moscow, Russia;V. Serbsky National Medical Research Centre of Psychiatry and Narcology, 119034 Moscow, Russia;

关键词: metabolome;    rats;    depressive-like behavior;    hippocampus;    frontal cortex;   

DOI  :  10.3390/ijms22179598

来源: DOAJ

【 摘 要 】

Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

【 授权许可】

Unknown