Abstract
It has been reported that systemic activation of D1 receptors promotes emergence from isoflurane-induced unconsciousness, suggesting that the central dopaminergic system is involved in the process of recovering from general anesthesia. The nucleus accumbens (NAc) contains abundant GABAergic medium spiny neurons (MSNs) expressing the D1 receptor (D1R), which plays a key role in sleep–wake behavior. However, the role of NAc D1 receptors in the process of emergence from general anesthesia has not been identified. Here, using real-time in vivo fiber photometry, we found that neuronal activity in the NAc was markedly disinhibited during recovery from propofol anesthesia. Subsequently, microinjection of a D1R selective agonist (chloro-APB hydrobromide) into the NAc notably reduced the time to emerge from propofol anesthesia with a decrease in δ-band power and an increase in β-band power evident in the cortical electroencephalogram. These effects were prevented by pretreatment with a D1R antagonist (SCH-23390). Whole-cell patch clamp recordings were performed to further explore the cellular mechanism underlying the modulation of D1 receptors on MSNs under propofol anesthesia. Our data primarily demonstrated that propofol increased the frequency and prolonged the decay time of spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature IPSCs (mIPSCs) of MSNs expressing D1 receptors. A D1R agonist attenuated the effect of propofol on the frequency of sIPSCs and mIPSCs, and the effects of the agonist were eliminated by preapplication of SCH-23390. Collectively, these results indicate that modulation of the D1 receptor on the activity of NAc MSNs is vital for emergence from propofol-induced unconsciousness.
Similar content being viewed by others
Data Availability
All data are provided in the manuscript.
References
Hight DF, Dadok VM, Szeri AJ, Garcia PS, Voss L, Sleigh JW (2014) Emergence from general anesthesia and the sleep-manifold. Front Syst Neurosci 8:146. https://doi.org/10.3389/fnsys.2014.00146
Chidambaran V, Sadhasivam S, Diepstraten J, Esslinger H, Cox S, Schnell BM, Samuels P, Inge T, Vinks AA, Knibbe CA (2013) Evaluation of propofol anesthesia in morbidly obese children and adolescents. BMC Anesthesiol 13:8. https://doi.org/10.1186/1471-2253-13-8
Pandin P, Estruc I, Van Hecke D, Truong HN, Marullo L, Hublet S, Van Obbergh L (2019) Brain aging and anesthesia. J Cardiothorac Vasc Anesth 33(Suppl 1):S58–S66. https://doi.org/10.1053/j.jvca.2019.03.042
Cascella M, Bimonte S, Muzio MR (2018) Towards a better understanding of anesthesia emergence mechanisms: research and clinical implications. World J Methodol 8(2):9–16. https://doi.org/10.5662/wjm.v8.i2.9
Franks NP, Zecharia AY (2011) Sleep and general anesthesia. Can J Anaesth 58(2):139–148. https://doi.org/10.1007/s12630-010-9420-3
Zhong H, Tong L, Gu N, Gao F, Lu Y, Xie RG, Liu J, Li X, Bergeron R, Pomeranz LE, Mackie K, Wang F, Luo CX, Ren Y, Wu SX, Xie Z, Xu L, Li J, Dong H, Xiong L, Zhang X (2017) Endocannabinoid signaling in hypothalamic circuits regulates arousal from general anesthesia in mice. J Clin Investig 127(6):2295–2309. https://doi.org/10.1172/JCI91038
Du WJ, Zhang RW, Li J, Zhang BB, Peng XL, Cao S, Yuan J, Yuan CD, Yu T, Du JL (2018) The locus coeruleus modulates intravenous general anesthesia of zebrafish via a cooperative mechanism. Cell Rep 24(12):3146–3155. https://doi.org/10.1016/j.celrep.2018.08.046
Muller CP, Pum ME, Amato D, Schuttler J, Huston JP, Silva MA (2011) The in vivo neurochemistry of the brain during general anesthesia. J Neurochem 119(3):419–446. https://doi.org/10.1111/j.1471-4159.2011.07445.x
Monti JM, Monti D (2007) The involvement of dopamine in the modulation of sleep and waking. Sleep Med Rev 11(2):113–133. https://doi.org/10.1016/j.smrv.2006.08.003
Oishi Y, Lazarus M (2017) The control of sleep and wakefulness by mesolimbic dopamine systems. Neurosci Res 118:66–73. https://doi.org/10.1016/j.neures.2017.04.008
Kenny JD, Taylor NE, Brown EN, Solt K (2015) Dextroamphetamine (but not atomoxetine) induces reanimation from general anesthesia: implications for the roles of dopamine and norepinephrine in active emergence. PLoS ONE 10(7):e0131914. https://doi.org/10.1371/journal.pone.0131914
Taylor NE, Chemali JJ, Brown EN, Solt K (2013) Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia. Anesthesiology 118(1):30–39. https://doi.org/10.1097/ALN.0b013e318278c896
Taylor NE, Van Dort CJ, Kenny JD, Pei J, Guidera JA, Vlasov KY, Lee JT, Boyden ES, Brown EN, Solt K (2016) Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia. Proc Natl Acad Sci USA 113(45):12826–12831. https://doi.org/10.1073/pnas.1614340113
Solt K, Van Dort CJ, Chemali JJ, Taylor NE, Kenny JD, Brown EN (2014) Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia. Anesthesiology 121(2):311–319. https://doi.org/10.1097/ALN.0000000000000117
Ross S, Peselow E (2009) The neurobiology of addictive disorders. Clin Neuropharmacol 32(5):269–276
Dalley JW, Fryer TD, Brichard L, Robinson ES, Theobald DE, Laane K, Pena Y, Murphy ER, Shah Y, Probst K, Abakumova I, Aigbirhio FI, Richards HK, Hong Y, Baron JC, Everitt BJ, Robbins TW (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315(5816):1267–1270. https://doi.org/10.1126/science.1137073
Salgado S, Kaplitt MG (2015) The nucleus accumbens: a comprehensive review. Stereotact Funct Neurosurg 93(2):75–93. https://doi.org/10.1159/000368279
Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E, Girault JA (2008) Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. J Neurosci 28(22):5671–5685. https://doi.org/10.1523/jneurosci.1039-08.2008
Qiu MH, Vetrivelan R, Fuller PM, Lu J (2010) Basal ganglia control of sleep-wake behavior and cortical activation. Eur J Neurosci 31(3):499–507. https://doi.org/10.1111/j.1460-9568.2009.07062.x
Qiu MH, Liu W, Qu WM, Urade Y, Lu J, Huang ZL (2012) The role of nucleus accumbens core/shell in sleep-wake regulation and their involvement in modafinil-induced arousal. PLoS ONE 7(9):e45471. https://doi.org/10.1371/journal.pone.0045471
Luo YJ, Li YD, Wang L, Yang SR, Yuan XS, Wang J, Cherasse Y, Lazarus M, Chen JF, Qu WM, Huang ZL (2018) Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 receptors. Nat Commun 9(1):1576. https://doi.org/10.1038/s41467-018-03889-3
Glen JBI (2018) The discovery and development of propofol anesthesia: the 2018 Lasker-DeBakey clinical medical research award. JAMA 320(12):1235–1236. https://doi.org/10.1001/jama.2018.12756
Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, Boston
Wang Y, Yu T, Yuan C, Yuan J, Luo Z, Pan Y, Zhang Y, Zhang Y, Yu B (2016) Effects of propofol on the dopamine, metabolites and GABAA receptors in media prefrontal cortex in freely moving rats. Am J Transl Res 8(5):2301–2308
Li Y, Zhong W, Wang D, Feng Q, Liu Z, Zhou J, Jia C, Hu F, Zeng J, Guo Q, Fu L, Luo M (2016) Serotonin neurons in the dorsal raphe nucleus encode reward signals. Nat Commun 7:10503. https://doi.org/10.1038/ncomms10503
Zhou Y, Wang X, Cao T, Xu J, Wang D, Restrepo D, Li A (2017) Insulin modulates neural activity of pyramidal neurons in the anterior piriform cortex. Front Cell Neurosci 11:378. https://doi.org/10.3389/fncel.2017.00378
Luo T, Yu S, Cai S, Zhang Y, Jiao Y, Yu T, Yu W (2018) Parabrachial neurons promote behavior and electroencephalographic arousal from general anesthesia. Front Mol Neurosci 11:420. https://doi.org/10.3389/fnmol.2018.00420
Fu B, Liu C, Zhang Y, Fu X, Zhang L, Yu T (2017) Ketamine attenuates the glutamatergic neurotransmission in the ventral posteromedial nucleus slices of rats. BMC Anesthesiol 17(1):111. https://doi.org/10.1186/s12871-017-0404-5
Hopf FW, Cascini MG, Gordon AS, Diamond I, Bonci A (2003) Cooperative activation of dopamine D1 and D2 receptors increases spike firing of nucleus accumbens neurons via G-protein betagamma subunits. J Neurosci 23(12):5079–5087
Le Moine C, Bloch B (1996) Expression of the D3 dopamine receptor in peptidergic neurons of the nucleus accumbens: comparison with the D1 and D2 dopamine receptors. Neuroscience 73(1):131–143
Monti JM, Fernandez M, Jantos H (1990) Sleep during acute dopamine D1 agonist SKF 38393 or D1 antagonist SCH 23390 administration in rats. Neuropsychopharmacology 3(3):153–162
Trampus M, Ferri N, Monopoli A, Ongini E (1991) The dopamine D1 receptor is involved in the regulation of REM sleep in the rat. Eur J Pharmacol 194(2–3):189–194. https://doi.org/10.1016/0014-2999(91)90104-x
Fu B, Yu T, Yuan J, Gong X, Zhang M (2017) Noradrenergic transmission in the central medial thalamic nucleus modulates the electroencephalographic activity and emergence from propofol anesthesia in rats. J Neurochem 140(6):862–873. https://doi.org/10.1111/jnc.13939
Munoz B, Yevenes GE, Forstera B, Lovinger DM, Aguayo LG (2018) Presence of inhibitory glycinergic transmission in medium spiny neurons in the nucleus accumbens. Front Mol Neurosci 11:228. https://doi.org/10.3389/fnmol.2018.00228
McDougall SJ, Bailey TW, Mendelowitz D, Andresen MC (2008) Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS). Neuropharmacology 54(3):552–563. https://doi.org/10.1016/j.neuropharm.2007.11.001
Eckle VS, Rudolph U, Antkowiak B, Grasshoff C (2015) Propofol modulates phasic and tonic GABAergic currents in spinal ventral horn interneurones. Br J Anaesth 114(3):491–498. https://doi.org/10.1093/bja/aeu269
Li J, Yu T, Shi F, Zhang Y, Duan Z, Fu B, Zhang Y (2018) Involvement of ventral periaqueductal gray dopaminergic neurons in propofol anesthesia. Neurochem Res 43(4):838–847. https://doi.org/10.1007/s11064-018-2486-y
Podda MV, Riccardi E, D’Ascenzo M, Azzena GB, Grassi C (2010) Dopamine D1-like receptor activation depolarizes medium spiny neurons of the mouse nucleus accumbens by inhibiting inwardly rectifying K+ currents through a cAMP-dependent protein kinase A-independent mechanism. Neuroscience 167(3):678–690. https://doi.org/10.1016/j.neuroscience.2010.02.075
Bass CE, Grinevich VP, Kulikova AD, Bonin KD, Budygin EA (2013) Terminal effects of optogenetic stimulation on dopamine dynamics in rat striatum. J Neurosci Methods 214(2):149–155. https://doi.org/10.1016/j.jneumeth.2013.01.024
Yin L, Li L, Deng J, Wang D, Guo Y, Zhang X, Li H, Zhao S, Zhong H, Dong H (2019) Optogenetic/chemogenetic activation of gabaergic neurons in the ventral tegmental area facilitates general anesthesia via projections to the lateral hypothalamus in mice. Front Neural Circ 13:73. https://doi.org/10.3389/fncir.2019.00073
Dobbs LK, Kaplan AR, Lemos JC, Matsui A, Rubinstein M, Alvarez VA (2016) Dopamine regulation of lateral inhibition between striatal neurons gates the stimulant actions of cocaine. Neuron 90(5):1100–1113. https://doi.org/10.1016/j.neuron.2016.04.031
Kohnomi S, Ebihara K, Kobayashi M (2017) Suppressive regulation of lateral inhibition between medium spiny neurons via dopamine D1 receptors in the rat nucleus accumbens shell. Neurosci Lett 636:58–63. https://doi.org/10.1016/j.neulet.2016.10.049
Qu WM, Huang ZL, Xu XH, Matsumoto N, Urade Y (2008) Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. J Neurosci 28(34):8462–8469. https://doi.org/10.1523/JNEUROSCI.1819-08.2008
Acknowledgements
An early version of this manuscript was presented in the Best of Abstracts (Basic Science) session in the American Society Anesthesiologists (ASA) annual meeting 2019. We thank all individuals who took part in this research.
Funding
This research was supported by grants from the National Natural Science Foundation of China (NSFC, Grant Nos. 81560237 and 81860204).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no potential conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhang, Y., Gui, H., Duan, Z. et al. Dopamine D1 Receptor in the Nucleus Accumbens Modulates the Emergence from Propofol Anesthesia in Rat. Neurochem Res 46, 1435–1446 (2021). https://doi.org/10.1007/s11064-021-03284-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-021-03284-3