Anti-post-traumatic stress disorder effect of dopamine D3 receptor antagonist

OBJECTIVE To explore the antipost-traumatic-stress-disorder(PTSD) effects and its probable mechanism of YQA14,a dopamine D3 receptor antagonist.METHODS Two PTSD animal models,the rat single prolonged stress(SPS) model and the mouse pre-shock model,were used in this experiment.In the SPS model,adult male Sprague-Dawley(SD) rats were randomly divided into control group,model group,positive group and YQA14 groups with different dosages.In the mouse pre-chock model,dopamine D3 receptor knockout(KO) and wild type(WT) mice were randomly divided into control group,model group,positive group and YQA14 group.After the establishment of animal models,the saline,sertraline(ig) and YQA14(ip)were administered to the animals in the control,model,positive control and test groups respectively.The open field test(OFT) was used to evaluate the locomotor activity while the contextual freezing(CF) measurement and elevated plus maze(EPM) test were used to evaluate the PTSD-like behaviors.RESULTS In the rat SPS model,neither SPS nor drug treatment affected the locomotor activity in rats.However,SPS rats showed significant PTSD-like behaviors with enhanced freezing time in CF(P<0.01) and decreased percentage of entries into open arms and time spent in open arms in EPM(P<0.05,P<0.01).Moreover,compared with the model group,the repeated administration of YQA14(3.125,6.25 and 12.5 mg·kg-1)significantly reduced the freezing time(P<0.01)and increased the percentages of entries into open arms and time spent in open arms(P<0.05).In the mouse pre-shock model,when both model groups showed significant higher freezing time compared with the respective control groups(P<0.05,P<0.01),YQA14 selectively alleviated the freezing time on WT mice(P<0.05) while had no effect on KO mice.In the EPM tests,the WT mice model group showed a significant reduction in the percentage of entries into open arms and time spent in open arms(P<0.05) while D3 R KO mice model group didn′ t show any reduction,compared with respective control groups.Furthermore,daily administration of YQA14 at 12.5 mg·kg-1 both significantly reduced the percentages of entries into and time spent in open arms(P<0.05) but not D3 R KO mice.None of the locomotor activity were significantly affected.CONCLUSION YQA14 could significantly alleviate the PTSD-like behaviors in rodents and the effects were mediated by the blockade of brain D3 receptors.