Behavior Effect And Its Possible Mechanism Of Action Of Oleamide On Social-isolated Mice

Animal models are important tools for the advancement of medicine, and have increasing importance in psychiatric studies. Social isolation of rodents is used to mimic human psychopathological processes, such as depression and anxiety. Investigation of the pattern of behavioral changes in mice reared in isolation may help our understanding of the aetiology of human anxiety and depression disorders.The present studies demonstrated that social-isolated mice produced the anxiogenic and aggressive profile by using the elevated plus-maze test, the light/dark test, the hole-board test. Treatment with several drugs, including oleamide, baicalin and Panaxquin quefoliuml saponin (PQS) produced the anxiolytic and anti-aggressive effects in social-isolated mice. In addition, the result also showed that oleamide and baicalin had an antidepressant-like effect in social-isolated mice by using two depressive models in mice, i.e. forced swimming test (FST) and tail suspension test (TST).Oleamide (cis-9,10-octadecenoamide) is an endogenous sleep-inducing substance, first isolated from the cerebrospinal fluid of sleep-deprived cats. In recent years, accumulating evidence supports that oleamide is an endogenous signaling factor and has many pharmacological activities. But the mechanism of action of oleamide in the central nervous system remains unclear.To further explore the mechanisms of action underlying the anxiolytic and anti-depressant activities of oleamide, 5-HT_1A, 5-HT_2A and GABA_a receptor expression were determined in the hippocampal and prefrontal cortex of the mice by using western blot analysis and immunohistochemical technique. The results showed that expression of 5-HT_1A and 5-HT_2A receptors was increased and expression of GABA_A receptor was decreased in social-isolated mice, which could be reversed by oleamide. Thus, we suggested that the anxiolytic and anti-depressive effect of oleamide may be related with serotonergic and GABAergic receptors.Proteomic technique is now obviously the overwhelming used method in studies of proteins differentially expressed in altered conditions. In the present study, proteomic analysis by two-dimensional gel electrophoresis (2-DE) together with mass spectrometry (MS) was applied to compare hippocampus and prefrontal cortex protein profiles among different groups [group-housed mice(GH),social-isolated mice(SI),SI+oleamide20mg/kg]. After differential analysis and identification by MALDI-TOF/MS, structural proteins [tubulin, neurofilaments protein M (NF-M) and tropomyosin gamma (TPM3)], enzymes with various catalytic activities [ATP synthase, enolase, isocitrate dehydrogenase (IDH3A), Ubiquinol-cytochrome-c reductase complex core protein I (UQCR1)], signal associated protein [guanine nucleotide dissociation inhibitor (GDI), Protein kinase C inhibitor protein 1(14-3-3 protein zeta/delta)], heat shock protein 47 (HSP47) were found differentially expressed between hippocampus in social-isolated and group-housed mice, and some of them could be reversed by oleamide. The results of proteomics settled the foundation for further studying the molecular mechanism of social isolation and the role of oleamide.In conclusion, the report studied the effect of behavioral changes of several drugs, especially oleamide, the effect of receptors and proteomic changes of oleamide on social-isolatded mice. It offers scientific proofs for the study of mechanism of anxiety and depression and correlated effect of drugs by using the social-isolated model.