Involvement Of VPAG Dopaminergic Neurons In Isoflurane-induced Loss And Recovery Of Consciousness

Objective: General anesthesia has been existed for 170 years,but its mechanism still remain unclear.More and more researchers nowadays tend to use the neural network theory to explain the action of narcotic drugs during general anesthesia.At present,it is believed that a variety of neurotransmitters and neural pathways in the brain involve in the generation and modulation of general anesthesia.Recent study showed that specific activation of dopamine neurons in the ventral tegmental area(VTA)can accelerate the recovery of consciousness induced by isoflurane.It indicated that dopaminergic pathways play an important role in promoting the recovery of general anesthesia by mean of shortening the time of recovery of righting reflex.The ventral periaqueductal gray area(v PAG)is the main locus of dopaminergic neurons which is closely related to the sleep-awake system of organisms.However,it is not clear whether v PAG has the same effect on the recovery of general anesthesia.For this reason,we have evaluated the loss of righting reflex time and recovery of righting reflex time after isoflurane administration in rats which are microinjected of 6-OHDA damaging dopaminergic neurons.Subsequently,we recorded brain waves of rats in isoflurane-induced loss and recovery of consciousness using EEG recording techniques in vivo to observe the effect of isoflurane on dopaminergic neurons of v PAG nucleus.The aim of this study is to investigate whether the dopamine neurons in the v PAG nucleus are involved in the promoting effect of the isoflurane-induced loss and recovery of consciousness.Methods: The adult male SD rats(260-300g)were divided into the6-OHDA-lesioned group(n=8)and the control group.Rats in the6-OHDA-lesioned group received 1?l 6-OHDA(4?g/?l)in their left of v PAG nucleus and electroencephalogram monitoring electrode in the cerebral cortex,while rats in the control group received 1?l saline and electroencephalogram monitoring electrode in the cerebral cortex.Two weeks later,those rats received the following experiment.The two groups of rats were anesthetized in the anesthesia box filled with oxygen in a flow rate of 1.5 L/min and isoflurane(1.5%).Stop inhalation of volatile anesthetics after 15 minutes of isoflurane administration,we recorded the loss of righting reflex time and recovery of righting reflex time,also the changes of EEG.Result:(1)Compared to the saline group,microinjections of 1?l 6-OHDA in the v PAG could significantly shorten the loss of righting reflex time(132.75±19.05 s vs222.00±48.79s)(p<0.05).Compared to the saline group,microinjections of 1?l6-OHDA in the v PAG could significantly prolong the recovery of righting reflex time(255.88±53.64 s vs 179.50±34.92s)(p<0.05).(2)Compared to the saline group,microinjections of 1?l 6-OHDA in the v PAG increased ? waves(48.92±1.72 s vs 44.51±1.84s)and ? waves(20.66±0.63 s vs15.62±0.93s)of EEG(p<0.05)and reduced ? waves(12.90±0.78 s vs 15.95±1.38s)and ? waves(11.60±0.58 s vs 15.98±2.59s).Conclusion: Dopaminergic neurons of the v PAG nucleus have a certain role in isoflurane-induced loss and recovery of consciousness.