Preliminary Study On The Antidepressant Effect And Its Possible Mechanism Of New Pentapeptide Drug XMT

Objective: To research the effect of XMT on depression and preliminary explore itspossible mechanism.Methods:1. The tail suspension test in mice, the forced swimming test in mice and thechronically unpredictably mildly stressed model in rats were used to research theantidepressant effect of XMT.2. The behavioral and pharmacological models (such as5-HTP induced mouse head-twitch test and yohimbine toxicity potentiation test) andhigh performance liquid chromatography with electrochemical detector (HPLC-ECD) totest the content of monoamine and metabolite in prefrontal cortex of CUMS rats wereused to study the antidepressant mechanism of XMT on monoaminergic system.3. TheELISA method was used to test the serum concentration of adrenocorticotropic hormone(ACTH) and corticosterone (CORT) in CUMS rats in order to study the antidepressantmechanism of XMT on HPA aix system.4. The morris water maze test was used toevaluate the effect of XMT on learning and memory dysfunction in CUMS rats.Results:1. In the tail suspension and forced swimming tests in mice, XMT couldsignificantly reduced the immobility time, while there was no obviously stimulant effecton the locomotor activity, which depleted the false positive result. These resultsindicated that there was antidepressant effect of XMT on behavioural despair models inmice.2. The treatment with XMT for4weeks could significantly increase the sucrosepreference, the crossing and rearing scores of open-field test, and the body weight ofCUMS rats, which showed that XMT could reverse the depression-like behaviors suchas anhedonia, activity reduction, interest loss and weight lessen induced by CUMS.These results indicated that there was antidepressant effect of XMT on CUMS rats.3. In5-HTP induced head-twitch test, XMT could significantly decrease the5-HTP inducedhead-twitch response in mice, while it had no effect on the yohimbine toxicity, whichshowed that the antidepressant effect of XMT may be related to serotonin system.4.The contents of5-HT and DA in prefrontal cortex of CUMS rats were increased byXMT, and the ratios of5-HT/5-HIAA and DA/DOPAC were also significantly increased,which showed that XMT could reduce the transformation ratio of5-HT and DA and theantidepressant effect may be related to the property of MAOIs.5. The treatment with XMT for4weeks could significantly decrease the concentration of blood serum ACTHand CORT in CUMS rats, which showed that the antidepressant effect of XMT may berelated to the HPA aix.6. In Morris water maze test, XMT could increase the timescross target, the total time and distance in target quadrant of CUMS rats, which showedthat XMT could relieve CUMS rats’ memory and recognition dysfunction in extent.Conclusion:1. XMT shows antidepressant-like effect in behavioral despair model inmice and CUMS depression model in rats.2. The antidepressant mechanism of XMTmay be related to the serotonin system, the HPA axis and so on.3. XMT can reverse thelearning and memory dysfunction caused by CUMS to some extent.