Study On The Role Of The Locus Ceruleus Norepinephrine Neurotransmitters In The Loss/recovery Of Consciousness Induced By Propofol Anesthesia

Background The mechanism of loss of consciousness and recovery after general anesthesia and the target of anesthetics is still unclear.Recent research has shown that the locus ceruleus(LC)noradrenergic system plays an important role in regulating sleep and wakefulness.The norepinephrine(NE)released from LC is an important neurotransmitter in the regulation of wakefulness.However,how propofol affects NE changes in the central nervous system and the behavioral changes associated with this change are rarely reported.In this study,we used the methods of microdialysis and pharmacogenetics to study the NE involvement in the loss and recovery of consciousness in propofol anesthesia in LC region in ratsMethods1.12 healthy adult male SD rats were randomly divided into control group and propofol group(n=6).After the LC microdialysis models were established,the NE contents in LC were measured.The NE content under awaking state was set as the basal level in each group.At the time of ending basal level collected,a single inducing dose of propofol(11 mg/kg)was injected through tail vein,the rats were continuous infused with propofol(40 mg/kg/h)1h after the loss of righting reflex(LORR),and the CSF was collected for another 1 hour after resumption of righting reflex(RORR),the control group was given same amount of saline,each sample was collected every 30 min.2.Pharmacogenomics method was employed to verify the behavior change after change the NE release in LC of rats.Construction of specific activation(h M3Dq)and inhibitory(h M4Di)LC-NE neurons,The different Adeno-Associated Virus(AAV)was microinjected in LC area and ACSF in control group,3 weeks later,using microdialysis to measure the NE content in LC.3.After continuous intravenous infusion of propofol in maintenance dose,the time of LORR and RORR in h M3Dq、h M4 Di and control group was recorded 7 days later,the time of LORR and RORR after intraperitoneal injection CNO was measured.Results1.Propofol reduced NE content in LC extracellular fluid(P<0.05);2.Propofol reduced the HVA and DOPAC levels in the extracellular fluid of LC,and decreased the level of 5-HT(P<0.05),but had no effect on the 5-HIAA(P>0.05);3.Specific activation LC-NE neurons increased the content of NE in LC extracellular fluid(P<0.05)and inhibition them decreased the content of NE(P<0.05);4.Compared with control group,the content of NE in LC was increased,the RORR was decreased(P<0.05),but LORR was not altered(P>0.05);the content of NE in LC was decreased,the behavioral of LORR was decreased(P<0.05),RORR showed no statistical significance(P>0.05)Conclusion1.Propofol affects the level of NE in LC area;Alterations of NE content in the LC change the efficacy of propofol;2.LC adrenergic neurons participate in the process of loss and recovery of consciousness induced by propofol anesthesia.