Dopamine Receptors And NMDA Receptors Function In The Nucleus Accumbens Neurons Medium Spinous Characteristics Of

Nucleus accumbens (NAc) located in the ventral striatum can both accecpt the glutamatergic from prefrontal cortex (PFC) and the dopaminergic fromventral tegmental area (VTA). We can usually define the NAc into two parts namelyshell and core based on the Fiber orientation and the histology characteristics of cells. These two parts plays different roles in drug addiction. The core mainly involved in voluntary movement regulation, learning and performing Operant conditioning which act as the dorsal striatum, while the shell is the part which is sensitive to the effect of drug addiction,mainly involved in visceral movement regulation and the progress of Emotional control motivation that plays a simliar role as amygdaloid nucleus.Medium spiny neurons are the principal cells of the NAc, which take up about90%-95%of the total cell amountDrug addiction is a recrudescent chronic brain disease which can make the addict use the drug continually regardless and compulsively, this disease caused by the abused drugs which affect the reward system. Mesolimbic dopaminergic system (MLDS) is the structure foundation of the rewarding that make by drug addiction, MLDS mostly invovled in all the rewarding caused by the drug addiction, MLDS contains VTA、DA neuron and its project、NAc、amygdaloid nucleus and PFC, the VTA and NAc is the main nuclei oflaterleminiscus which show the rewarding. The Drug addiction can induce the changes of NAc of reward’s neurotransmitter. After withdrawal of opioid drugs, the specialization of Nervous system caused by NAc is regarded as a key mechanism of drug dependence. The specialization of Nervous system mainly contains the changes of synaptic plasticity and the discharge characteristics of neuron.Our previous research find that the active NMDAR can significantly enhance excitability and adaptability of in the Shell of NAc (NAcShell MSNs). The activing NR2A-containing NMDARs can enhance the adaptability of cell and the activing NR2B-containing NMDARs can enhance the excitability of cell, respectively. In fact, some research have showed that dopamine can enhance the excitability of the medium spiny neurons of the NAc and the NMDAR not only plays a key role in synaptic plasticity but also plays a important role in the discharge characteristics of neuron. NAc can both accecpt the glutamatergic from PFC and the dopaminergic from VTA, but until now it is unclear that whether there is interplay between these two neurotransmitters.In this work, we employed whole-cell patch-clamp recordings, and after perfuse different agonists or antagonists, we observe the interplay between the receptor subunits of NMDAR and DAR. To Provide theoretical reference for the study of the mechanism of drug addiction from the study of interplay between the receptor subunits in the chracters of the discharge characteristics of neuron and further providing the possible targets for the drug therapy of neurological diseases. The results of this work are as follows:1Continuously activated DAR can significantly inhibit the effect which caused by the activated NMDAR located in NAcShell MSNs.Firstly, we repeat our previous work and verified that NMDAR can significantly enhance the Excitability and adaptability of NAcShell MSNs. The activing NR2A-containing NMDARs can enhance the adaptability of cell and the activing NR2B-containing NMDARs can enhance the Excitability of cell, respectively. Based on this research, perfusion DA can significantly inhibit the effect caused by NMDAR which located in NAcShell MSNs, suggesting that the activated DAR inhibit the effect caused by NMDAR.2Blocking Dl-like receptor while perfusing DA almost have no influence on the effect caused by the activatedNR2A-containing NMDARs located in NAcShell MSNs.For the purpose to inhibit the activity of NR2B-containing NMDARs, we add Ro25-6981(3μM) to the liquid ACSF which contains PTX(100μM) and DNQX(10μM), further we add SCH23390(10μM) to inhibit the activity of D1-like receptor, then record once. We add20μM DA and add10μM NMDA after5min, record it again after20min. the results have showed that there is no significant changes in the rheobase and the number of evoked spikes between these two group wchich suggest that D2-like receptor have little influence on the effect of NR2A-containing NMDARs and DA inhibit NR2A-containing NMDARs though the D1-like receptor.3Blocking D2-like receptor while perfusing DA almost have no influence on the effect caused by the activated NR2A-containing NMDARs located in NAcShell MSNs.For the purpose to inhibit the activity of NR2A-containing NMDARs, we add NVP-AAM077to the the liquid ACSF which contains PTX(100μM) and DNQX(10μM), further we add Sulpiride to inhibit the activity of D2-like receptor, then record once. We add20μM DA and add10μM NMDA after5min, record it again after20min. the results have showed that there is no significant changes in the rheobase the number of evoked spikes and the spike train duration between these two group which suggest activating D1-like receptor and NR2B-containing NMDARs have little influence on the Excitability of NAcShell MSNs and the activating D1-like receptor inhibit NR2B-containing NMDARs.4Activating D2-like receptor though the perfusing quinpirole have no influence on the effect caused by NR2B-containing NMDARs located in NAcShell MSNs.We use the whole-cell patch-clamp recordings of NAcShell MSNs and we add NVP-AAM077to the liquid ACSF which contains PTX(100μM) and DNQX(10μM) to inhibit the activity of NR2A-containing NMDARs, then record once. Further we add the selective agonist of D2-like receptor to activate it, add10μM NMDA after5min, record it again after20min. the results have showed that there is no significant changes in the rheobase,spikes number and he spike train duration between these two group wchich suggest activating D2-like receptor and NR2B-containing NMDARs have little influence on the excitability and adaptation of MSN and the activating D2-like receptor inhibit NR2B-containing NMDARs.Abvoe all, we can include that:Activating the DAR and NMDAR at the same time, there is no significant changes in the rheobase,spikes number and the spike train duration of NAcShell MSNs which suggest there is no changes in the excitability and adaptation of neuron and the activating DAR inhibit NMDAR. Our further work also show that the D1-like receptor inhibit NR2A or NR2B-containing NMDARs and activating D2-like receptor inhibit NR2B-containing NMDARs.