Research Advancements in the Role of the Brain Dopaminergic System in General Anesthesia

Wei LUO; Chengdong YUAN; Mengnan HAO; Jie ZHANG; Yi ZHANG

doi:10.3881/j.issn.1000-503X.16245

PDF(569 KB)

Acta Academiae Medicinae Sinicae ›› 2025, Vol. 47 ›› Issue (3) : 441-446. DOI: 10.3881/j.issn.1000-503X.16245

Review Articles

Research Advancements in the Role of the Brain Dopaminergic System in General Anesthesia

Wei LUO ¹^,² ,
Chengdong YUAN ¹^,² ,
Mengnan HAO ¹^,² ,
Jie ZHANG ¹ ,
Yi ZHANG ¹^,²

Author information +

History +

Abstract

General anesthesia is widely used in clinical practice,whereas the exact mechanism behind the general anesthetic-induced reversible loss of consciousness remains unclear.Recent studies have revealed a close relationship between the dopaminergic system and general anesthetic-induced loss of consciousness.This system,encompassing dopamine neurons,dopamine receptors,and related neural pathways,regulates functions such as movement,memory,arousal,and cognition.The dopaminergic neurons in the ventral periaqueductal gray and ventral tegmental area,along with D1 receptors,have been shown to facilitate emergence from anesthesia.However,the role of D2 receptors remains controversial.This review summarizes recent advancements in the role of the dopaminergic system in general anesthesia and the underlying mechanism,with the aim of clarifying the mechanism of general anesthesia and providing a theoretical basis for preventing delayed emergence from anesthesia.

Key words

dopaminergic system / general anesthesia / dopamine neuron / neural pathway / dopamine receptor

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

Wei LUO , Chengdong YUAN , Mengnan HAO , et al . Research Advancements in the Role of the Brain Dopaminergic System in General Anesthesia[J]. Acta Academiae Medicinae Sinicae. 2025, 47(3): 441-446 https://doi.org/10.3881/j.issn.1000-503X.16245

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis

[1]	Moody OA, Zhang ER, Vincent KF, et al. The neural circuits underlying general anesthesia and sleep[J]. Anesth Analg, 2021, 132(5):1254-1264.DOI:10.1213/ANE.0000000000005361. Cited in this article [1]

[2]	Alkire MT, Hudetz AG, Tononi G. Consciousness and anesthesia[J]. Science, 2008, 322(5903):876-880.DOI:10.1126/science.1149213. Cited in this article [1]

[3]	Hu JJ, Liu Y, Yao H, et al. Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus[J]. Nat Neurosci, 2023, 26(5):751-764.DOI:10.1038/s41593-023-01290-y. Cited in this article [1]

[4]	Franks NP. General anaesthesia:from molecular targets to neuronal pathways of sleep and arousal[J]. Nat Rev Neurosci, 2008, 9(5):370-386.DOI:10.1038/nrn2372. Cited in this article [1]

[5]	Hemmings HJ, Riegelhaupt PM, Kelz MB, et al. Towards a comprehensive understanding of anesthetic mechanisms of action:a decade of discovery[J]. Trends Pharmacol Sci, 2019, 40(7):464-481.DOI:10.1016/j.tips.2019.05.001. Cited in this article [1]

[6]	Engelhard B, Finkelstein J, Cox J, et al. Specialized coding of sensory,motor and cognitive variables in VTA dopamine neurons[J]. Nature, 2019, 570(7762):509-513.DOI:10.1038/s41586-019-1261-9. Cited in this article [2]

[7]	Wu M, Zhang X, Feng S, et al. Dopamine pathways mediating affective state transitions after sleep loss[J]. Neuron, 2024, 112(1):141-154.DOI:10.1016/j.neuron.2023.10.002. Cited in this article [1]

[8]	Chinta SJ, Andersen JK. Dopaminergic neurons[J]. Int J Biochem Cell Biol, 2005, 37(5):942-946.DOI:10.1016/j.biocel.2004.09.009. Cited in this article [1]

[9]	Islam K, Meli N, Blaess S. The development of the mesoprefrontal dopaminergic system in health and disease[J]. Front Neural Circuits, 2021,15:746582.DOI:10.3389/fncir.2021.746582. Cited in this article [1]

[10]	Watanabe H, Dijkstra JM, Nagatsu T. Parkinson’s disease:cells succumbing to lifelong dopamine-related oxidative stress and other bioenergetic challenges[J]. Int J Mol Sci, 2024, 25(4):2009.DOI:10.3390/ijms25042009. Cited in this article [1]

[11]	Gupta S, Bharatha A, Cohall D, et al. Aerobic exercise and endocannabinoids:a narrative review of stress regulation and brain reward systems[J]. Cureus, 2024, 16(3):e55468.DOI:10.7759/cureus.55468. Cited in this article [1]

[12]	Tomaso CC, Johnson AB, Nelson TD. The effect of sleep deprivation and restriction on mood,emotion,and emotion regulation:three meta-analyses in one[J]. Sleep, 2021, 44(6):zsaa289.DOI:10.1093/sleep/zsaa289. Cited in this article [1]

[13]	Grattan DR. 60 Years of neuroendocrinology:the hypothalamo-prolactin axis[J]. J Endocrinol, 2015, 226(2):T101-T122.DOI:10.1530/JOE-15-0213. Cited in this article [1]

[14]	Di T, Wang Y, Zhang Y, et al. Dopaminergic afferents from midbrain to dorsolateral bed nucleus of stria terminalis inhibit release and expression of corticotropin-releasing hormone in paraventricular nucleus[J]. J Neurochem, 2020, 154(2):218-234.DOI:10.1111/jnc.14992. Cited in this article [1]

[15]	Liu C, Zhou X, Zhu Q, et al. Dopamine neurons in the ventral periaqueductal gray modulate isoflurane anesthesia in rats[J]. CNS Neurosci Ther, 2020, 26(11):1121-1133.DOI:10.1111/cns.13447. Cited in this article [1]

[16]	Li J, Yu T, Shi F, et al. Involvement of ventral periaqueductal gray dopaminergic neurons in propofol anesthesia[J]. Neurochem Res, 2018, 43(4):838-847.DOI:10.1007/s11064-018-2486-y. Cited in this article [1]

[17]	Solt K, Van Dort CJ, Chemali JJ, et al. Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia[J]. Anesthesiology, 2014, 121(2):311-319.DOI:10.1097/ALN.0000000000000117.

[18]	Taylor NE, Van Dort CJ, Kenny JD, et al. Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia[J]. Proc Natl Acad Sci U S A, 2016, 113(45):12826-12831.DOI:10.1073/pnas.1614340113. Cited in this article [1]

[19]	Qiu G, Wu Y, Yang Z, et al. Dexmedetomidine activation of dopamine neurons in the ventral tegmental area attenuates the depth of sedation in mice[J]. Anesthesiology, 2020, 133(2):377-392.DOI:10.1097/ALN.0000000000003347.

[20]	Zhou X, Wang Y, Zhang C, et al. The role of dopaminergic VTA neurons in general anesthesia[J]. PLoS One, 2015, 10(9):e0138187.DOI:10.1371/journal.pone.0138187.

[21]	Li J, Li H, Wang D, et al. Orexin activated emergence from isoflurane anaesthesia involves excitation of ventral tegmental area dopaminergic neurones in rats[J]. Br J Anaesth, 2019, 123(4):497-505.DOI:10.1016/j.bja.2019.07.005.

[22]	Beaulieu JM, Gainetdinov RR. The physiology,signaling,and pharmacology of dopamine receptors[J]. Pharmacol Rev, 2011, 63(1):182-217.DOI:10.1124/pr.110.002642. Cited in this article [1]

[23]	Mishra A, Singh S, Shukla S. Physiological and functional basis of dopamine receptors and their role in neurogenesis:possible implication for Parkinson’s disease[J]. J Exp Neurosci, 2018,12:2083187275.DOI:10.1177/1179069518779829. Cited in this article [3]

[24]	Dziedzicka-Wasylewska M, Polit A, Błasiak E, et al. G protein-coupled receptor dimerization-What next[J]. Int J Mol Sci, 2024, 25(6):3089.DOI:10.3390/ijms25063089.

[25]	Lu Y, Hatzipantelis CJ, Langmead CJ, et al. Molecular insights into orphan G protein-coupled receptors relevant to schizophrenia[J]. Br J Pharmacol, 2024, 181(14):2095-2113.DOI:10.1111/bph.16221. Cited in this article [1]

[26]	Taylor NE, Chemali JJ, Brown EN, et al. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia[J]. Anesthesiology, 2013, 118(1):30-39.DOI:10.1097/ALN.0b013e318278c896. Cited in this article [1]

[27]	Zhang Y, Gui H, Hu L, et al. Dopamine D1 receptor in the NAc shell is involved in delayed emergence from isoflurane anesthesia in aged mice[J]. Brain Behav, 2021, 11(1):e01913.DOI:10.1002/brb3.1913. Cited in this article [2]

[28]	Song Y, Chu R, Cao F, et al. Dopaminergic neurons in the ventral tegmental-prelimbic pathway promote the emergence of rats from sevoflurane anesthesia[J]. Neurosci Bull, 2022, 38(4):417-428.DOI:10.1007/s12264-021-00809-2. Cited in this article [2]

[29]	Zhang Y, Gui H, Duan Z, et al. Dopamine D1 receptor in the nucleus accumbens modulates the emergence from propofol anesthesia in rat[J]. Neurochem Res, 2021, 46(6):1435-1446.DOI:10.1007/s11064-021-03284-3. Cited in this article [1]

[30]	Bao WW, Xu W, Pan GJ, et al. Nucleus accumbens neurons expressing dopamine D1 receptors modulate states of consciousness in sevoflurane anesthesia[J]. Curr Biol, 2021, 31(9):1893-1902.DOI:10.1016/j.cub.2021.02.011. Cited in this article [1]

[31]	Kato R, Zhang ER, Mallari OG, et al. D-amphetamine rapidly reverses dexmedetomidine-induced unconsciousness in rats[J]. Front Pharmacol, 2021,12:668285.DOI:10.3389/fphar.2021.668285. Cited in this article [1]

[32]	Araki R, Hayashi K, Sawa T. Dopamine D2-receptor antagonist droperidol deepens sevoflurane anesthesia[J]. Anesthesiology, 2018, 128(4):754-763.DOI:10.1097/ALN.0000000000002046 Cited in this article [1]

[33]	Niu L, Hao M, Wang Y, et al. Dopamine D2-receptor neurons in nucleus accumbens regulate sevoflurane anesthesia in mice[J]. Front Mol Neurosci, 2023,16:1287160.DOI:10.3389/fnmol.2023.1287160. Cited in this article [2]

[34]	Yang B, Ao Y, Liu Y, et al. Activation of dopamine signals in the olfactory tubercle facilitates emergence from isoflurane anesthesia in mice[J]. Neurochem Res, 2021, 46(6):1487-1501.DOI:10.1007/s11064-021-03291-4. Cited in this article [1]

[35]	Rogobete AF, Sandesc D. General anesthesia as a multimodal individualized clinical concept[J]. Medicina (Kaunas), 2022, 58(7):956.DOI:10.3390/medicina58070956. Cited in this article [1]

[36]	Dovonou A, Bolduc C, Soto LV, et al. Animal models of Parkinson’s disease:bridging the gap between disease hallmarks and research questions[J]. Transl Neurodegener, 2023, 12(1):36.DOI:10.1186/s40035-023-00368-8. Cited in this article [1]

[37]	Noursadeghi E, Haghparast A. Modulatory role of intra-accumbal dopamine receptors in the restraint stress-induced antinociceptive responses[J]. Brain Res Bull, 2023, 195:172-179.DOI:10.1016/j.brainresbull.2023.03.003. Cited in this article [1]

[38]	Wang J, Miao X, Sun Y, et al. Dopaminergic system in promoting recovery from general anesthesia[J]. Brain Sci, 2023, 13(4):538.DOI:10.3390/brainsci13040538. Cited in this article [1]

[39]	Shu SY, Bao XM, Ning Q, et al. New component of the limbic system:marginal division of the neostriatum that links the limbic system to the basal nucleus of meynert[J]. J Neurosci Res, 2003, 71(5):751-757.DOI:10.1002/jnr.10518. Cited in this article [1]

[40]	Li C, Li Y, Zhang W, et al. Dopaminergic projections from the hypothalamic A11 nucleus to the spinal trigeminal nucleus are involved in bidirectional migraine modulation[J]. Int J Mol Sci, 2023, 24(23):16876.DOI:10.3390/ijms242316876. Cited in this article [1]

[41]	Gui H, Liu C, He H, et al. Dopaminergic projections from the ventral tegmental area to the nucleus accumbens modulate sevoflurane anesthesia in mice[J]. Front Cell Neurosci, 2021,15:671473.DOI:10.3389/fncel.2021.671473. Cited in this article [1]

[42]	Guo J, Xu K, Yin JW, et al. Dopamine transporter in the ventral tegmental area modulates recovery from propofol anesthesia in rats[J]. J Chem Neuroanat, 2022,121:102083.DOI:10.1016/j.jchemneu.2022.102083. Cited in this article [1]

[43]	Cao F, Guo Y, Guo S, et al. Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia[J]. CNS Neurosci Ther, 2024, 30(3):e14675.DOI:10.1111/cns.14675. Cited in this article [1]

[44]	Zhu Y, Wang K, Ma T, et al. Nucleus accumbens D1/D2 circuits control opioid withdrawal symptoms in mice[J]. J Clin Invest, 2023, 133(18):e163266.DOI:10.1172/JCI163266. Cited in this article [1]

[45]	Zhang J, Peng Y, Liu C, et al. Dopamine D1-receptor-expressing pathway from the nucleus accumbens to ventral pallidum-mediated sevoflurane anesthesia in mice[J]. CNS Neurosci Ther, 2023, 29(11):3364-3377.DOI:10.1111/cns.14267. Cited in this article [1]

[46]	Wang D, Guo Y, Li H, et al. Selective optogenetic activation of orexinergic terminals in the basal forebrain and locus coeruleus promotes emergence from isoflurane anaesthesia in rats[J]. Br J Anaesth, 2021, 126(1):279-292.DOI:10.1016/j.bja.2020.09.037. Cited in this article [1]

[47]	Arrigoni E, Fuller PM. The sleep-promoting ventrolateral preoptic nucleus:what have we learned over the past 25 years[J]. Int J Mol Sci, 2022, 23(6):2905.DOI:10.3390/ijms23062905. Cited in this article [1]