Objective To investigate the effect of altered 2-arachidonoylglycerol(2-AG) levels on autistic behaviors in VPA-induced rats(ASD model), so as to provide evidence for identifying the etiology of ASD. Methods The rats were divided into CON group, VPA group(ASD), acute JZL184 injection group [VPA+40 mg/kg JZL184 group(VPA+40AJ)], chronic JZL184 injection group [including VPA+1 mg/kg JZL184 group(VPA+1RJ), VPA+3 mg/kg JZL184 group(VPA+3RJ) and VPA+10 mg/kg JZL184 group(VPA+10RJ) ]. The ASD-like behavior of rats in each group was assessed. The levels of endocannabinoids(eCBs) in the hippocampus of rats were detected by liquid chromatography-mass spectrometry. Western blot was used to test the expression levels of related receptors and metabolic enzymes in eCB system. Results The levels of 2-AG and AEA in VPA group were significantly lower than those in CON group(P<0.05). After JZL184 intervention, the levels of 2-AG in VPA+3RJ group and VPA+10RJ group significantly increased(P<0.05). Compared with the CON group, the number of buried marbles, self-grooming time and spontaneous activities increased significantly in VPA group, and the sociability index and the social preference index decreased(P<0.05). After JZL184 intervention, the number of buried marbles, self-grooming time and spontaneous activities decreased, and the sociability index and the social preference index in VPA+40AJ group increased significantly, the self-grooming time of the rats in VPA+1RJ group decreased. After JZL184 intervention, the number of buried marbles, self-grooming time and spontaneous activities decreased, and the social preference index of the rats in VPA+3RJ group increased significantly. The number of buried marbles and self-grooming time decreased, and the social preference index of the rats in VPA+10RJ group increased significantly(P<0.05).The protein expressions of CB1R, DAGL, MAGL and FAAH in VPA group were significantly higher than those in CON group(P<0.05).After JZL184 intervention, the protein expressions of DAGL and MAGL of the rats in VPA+3RJ group were significantly down-regulated, and MAGL in VPA+10RJ group were also significantly down-regulated(P<0.05). Conclusions Low eCBs signal is associated with autistic behaviors in VPA-induced rats, and boosting 2-AG levels can improve repetitive and stereotypical behaviors, hyperactivity and social functions in ASD rats.
Key words
autism spectrum disorder /
endocannabinoids /
VPA-induced rats /
JZL184
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