Dietary of n-3 polyunsaturated fatty acids influence neurotransmitter systems of rats exposed to unpredictable chronic mild stress.

Emerging evidence suggest that neuromodulators are the critical factor involved in depression. This study aimed to investigate the effects of unpredictable chronic mild stress (CUMS) and n-3 polyunsaturated fatty acids (n-3 PUFAs) on central nervous system. The depressive-like behaviors induced by CUMS were assessed by sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to quantify the levels of neurotransmitters and their metabolites involved in serotonergic, dopaminergic, noradrenergic, GABAergic neurotransmitter systems in hippocampus and prefrontal cortex. Repeated CUMS caused depressive-like behaviors of rats, associated with the alteration of neurotransmitters in brain, including the decreasing DA level, the increasing NE and GABA level, and the increasing 5-HT turnover rate in hippocampus, which could be partly alleviated by sufficient n-3 PUFAs supplementation. The influence of stress and diet on neurotransmitters in the prefrontal cortex was slight. However, it was obvious that supplementary of n-3 PUFAs relieved the decreasing DA/NE between-metabolite ratio 1,2 and DA/5-HT between-metabolite ratio 1,2 in the prefrontal cortex caused by CUMS. Altered neurotransmitter turnover rates and between-metabolite ratios in brain may be better predictors in depression and antidepressant treatment compared with monoamine neurotransmitters.