Study On The Related Mechanism Between Neuronal Dopamine Receptor In Nucleus Accumbens And The Recovery Of Propofol-induced Unconsciousness

Background and objective: Recent studies have found that intravenous administration of dopamine receptor agonists or electrical stimulation of the dopaminergic nucleus can make rats emergence from general anesthesia. Hence the dopaminergic neuronal pathway may get involved in the process of recovery from general anesthesia, but the mechanism is still unclear. Neurons in the nucleus accumbens(NAc) contain abundant dopamine D1 and D2 receptor, which widely receives most projection from the ventral tegmental area(VTA, a key area of mesolimbic dopaminergic systems). NAc contributes to multiple pathological and physiological processes such as drug addiction, rewarding and locomotor activity, Whether the nucleus accumbens is involved in the process of general anesthesia recovery is not reported in the literature. Therefore, this study utilized the methods of bilateral microinjection and patch-clamp technology to reveal the role of dopamine receptor in the recovery of propofol-induced unconsciousness, and analysis the effects of propofol on the neuronal spontaneous excitatory synaptic currents(s EPSC) in NAc neurons.Methods: 1. After NAc microinjection cannula was successfully implanted, 60 rats were randomly divided into two groups: D1 R group(n = 30) and D2 R group(n = 30). Both groups received propofol(11 mg/kg) through intravenous indwelling needle to produce loss of righting reflex(LORR), then the microinjection was performed. According to the grouping, normal saline, dopamine D1/D2 receptor agonist or antagonist were injected separately. The total volume of microinjection was 5 μg/side at a rate of 0.25 μl/min. The time of resumption of righting reflex(RORR) was recorded. After the end of the experiment, histological methods were carried out to verify the location of the microinjection cannula. 2. The whole-cell patch clamp mode was built in brain slices from SD rats(aged 7-14 postnatal days). With voltage clamped at-80 m V, the s EPSC of NAc neurons were recorded. The neurons were perfused with artificial cerebrospinal fluid(ACSF), propofol,dopamine receptor agonist(or antagonist) + propofol according to research purpose. Drugs were perfused for 5 min in all groups and data were recorded for 5 min.Results: 1. Dopamine D1 receptor agonists decreased the time of RORR after propofol-induced unconsciousness(P < 0.05), while D1 receptor antagonist increased the time of RORR(P < 0.05); 2. Nither Dopamine D2 receptor agonist nor antagonist had no significant effect on the time of RORR(P > 0.05); 3. Propofol 10 μM increased the frequency of s EPSC in NAc neurons(P < 0.05); 4. Dopamine D1 receptor agonists inhibited the propofol-induced elevation of the frequency of s EPSC(P < 0.05).Conclusion: 1. Dopamine D1 receptor in nucleus accumbens contributes to the recovery of propofol-induced unconsciousness; 2. Propofol enhance the glutamatergic transmission in NAc neurons; 3. Activation of dopamine D1 receptor decreases the enhancement of the glutamatergic transmission induced by propofol.