The Role And Regulation Of Neural Activity Of Nucleus Accumbens In The Process Of Self-Injury

Self-injury has been defined as direct and deliberate bodily harm in the absence of suicidal intent.Attention from social and medical research area on self-injury is increasing these years.The incidence of self-injury behavior in the total population is approximately 2?6%.Patients with psychological or neurological diseases have a higher incidence rate.The etiology of self-injury behavior is not clear yet,the physiological,psychological,social environment,and many other factors are involved in the pathogenesis of self-injury behavior(SIB).The nucleus accumbens(NAc)is a brain area in basal ganglia,which plays an important role in hatred,aggression,fear,pleasure,rewarding and reinforcement learning.The dopaminergic receptor mediated neurons of NAc receive the inhibitory projection from rewarding system mediated by ventral tegmental area,NAc also receives projection from lateral habenula which involved in regulation of fear memory,and regulate the activity of globus pallidus through a large number of D1 and D2-mediated dopaminergic receptor neurons.Our previous experiments found that inhibition of globus pallidum internus neurons induced SIB in rats.Therefore,we have reason to assume that NAc could regulate SIB through direct or indirect synaptic connection and rewarding mechanisms.In this thesis we will discuss the correlation between NAc and the pathogenesis of SIB by using pharmacological,electrophysiological,behavioral,and molecular biological technologies.Our experimental results are shown as follows:(1).Pharmacology experiments:A,Activation of globus pallidum internus(GPi)neurons by GABAA,GABAB,AMPA receptor agonists but not inhibition of GPi neurons by GABAA,GABAB,AMPA receptor inhibitors induced SIB in rats.B,Inhibition of GABAA neurons in ventral tegmental area(VTA)prevented SIB completely in rats,but activation GABAA neurons of VTA only reduced the incidence of SIB.C,Inhibition of GABAA neurons in Nucleus accumbens Shell(AcbSh)reduced SIB,while activation GABAA neurons of AcbSh completely prevented SIB;either activation or inhibition of GABAB neurons in AcbSh affacted SIB;Inhibition of GABAA neurons in Nucleus accumbens Core(AcbC)reduced the occurrence of SIB,activated the GABAA neurons in AcbC had no effects.D,Activation or inhibition of DIR and D2R in AcbSh did not reduce SIB in the presence of 1?g muscimol in GPi.Inhibition of D1R and D2R in AcbSh increased the incidence of SIB in the presence of 0.2?g muscimo in GPi.E,Neither activation nor inhibition of AcbSh neurons reduced the incidence of SIB without fear memory retrieval..(2).Behavioral experiments:Our behavioral experiments showed that short-term SIB did not affect the anxiety level of rats when tested in open field and elevated plus maze test.(3).Electrophysiological experimentsLocal field potential of ventral tegmental area,NAc,BLA,LHb,mPFC in the process of SIB changed significantly in free moving rats.,and the coherence between VTA-BLA,VTA-mPFC,BLA-mPFC and NAc-mPFC in 4-8Hz was decreased in SIB.(4).Molecular experiment:Western Blot showed that the expression of phosphorylated sites of Ser831 and Ser845 in GluR1 in NAc neurons increased and then decreased in the induction and maintenance of SIBIn summary:The activation of GABAA neurons in GPi can induce self-injury behavior,and the neuronal activities of VTA and NAc are involved in the regulation of SIB.The activities of D1 and D2-mediated dopaminergic receptor neurons,which inhibit Nucleus accumbens Shell,have a significant effect on the self-injury behavior,and the process of the retrieval of fear memory is also involved in the process of self-injury.Short term self-injury behavior(6h)did not affect the anxiety level in rats.In the process of self-injury behavior,VTA,NAc,BLA,LHb,mPFC in different frequency bands of the local field potential changed with of time.There was a significant correlation between VTA-BLA,VTA-mPFC,BLA-mPFC,and NAc-mPFC in these brain regions during the process of self-injury behavior.At the same time,in the process of self-injury behavior,Nucleus accumbens excitatory input and phosphorylation site Ser831 and Ser845 of GluR1 expression increased and then decreased with the initiation and maintenance of self-injury.Our experiments show that NAc is involved in the regulation of SIB by dopamine system through the interaction between these brain regions of VTA,BLA,LHb,and mPFC.