Neurotoxic Effects Of Typical Psychoactive Substances On Chinese Rare Minnow

Pharmaceutical and Personal Care Products(PPCPs)are a type of emerging organic pollutants in aquatic environment,which have posed a serious threat to the environment in the past decades.As members of PPCPs,psychoactive substances are particularly noteworthy but not fully studied,which have been paid more and more attention in recent years due to their properties such as bioaccumulation and biotoxicity.Psychoactive substance refers to the substance that can affect the mental and behavioral state of human body after being ingested.They can be divided into psychotropic drugs and illegal drugs.Psychoactive substances and their metabolites usually enter into aquatic environment after excretion from human body and lead to adverse effects on aquatic animals.However,it remains known about the neurotoxicity of psychoactive substances on fish up to date.In this study,the effects of two psychotropic drugs(alprazolam and lorazepam)and two illegal drugs(codeine and morphine),which have been identified as the main psychoactive substances in the aquatic environment were studied on neurochemicals and behaviors of Chinese rare minnow to reveal their neurotoxicity on fish.An analytical method was developed to simultaneously detect the 4 psychoactive substances and 24 neurochemicals which belong to including histaminergic,glutamatergic,cholinergic,serotonergic,catecholaminergic and adrenergic systems in fish by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).In the fish homogenate matrix,the method quantification limit is between0.28-1.97 ng·g^-1.The relative recovery and matrix effect are between 66.4-116.7%and60.2-129%,respectively.The exposure test indicated that exposure to the 4 psychoactive substances resulted in accumulation of these compounds in Chinese rare minnow.The bioconcentration factor(BCF)decreased with the increase of exposure concentration for all of the 4compounds.Alprazolam and lorazepam not only induced serotonin(5-HT)and dopamine(DA)along with the decrease of glutamic acid(Glu),but also depressed the motor activity of Chinese rare minnow although without significance.Meanwhile,exposure to codeine and morphine induced acetylcholine(ACh),dopamine(DA)and adrenaline(E),and promoted the anxiety response of Chinese rare minnow at low concentration of exposure.On the whole,the 4 psychoactive substances showed neurotoxic effects on Chinese rare minnow by disrupting neurochemicals and behaviors.The comprehensive neurotoxicity was also assessed by employment of Toxicological Priority Index(Tox Pi).The results revealed that the psychoactive substances studied have more potentials to affect cholinergic,serotonergic,catecholaminergic and adrenergic systems on Chinese rare minnow.Codeine showed the lowest neurotoxicity among the 4 psychoactive substances.Lorazepam and morphine posed relatively higher neurotoxicity at low and high concentration,respectively.While the neurotoxic effect of alprazolam was observed among the three.The study disclosed the neurotoxic effects of alprazolam,lorazepam codeine and morphine on fish as well as the possible mechanisms,and provided scientific basis for risk assessment in aquatic ecosystem.