Dopaminergic D1 receptors in nucleus basalis modulate recovery from propofol anesthesia in rats

Document Type: Original Article


1 Department of Anesthesiology, Hospital of Stamatology, Zunyi Medical University, Dalian road, Zunyi 563000, Guizhou, China

2 Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Dalian road 149, Zunyi 563000, Guizhou, China

3 Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Dalian road 149, Zunyi 563000, Guizhou, China


Objective(s): Melatonin, an important hormone secreted by the epiphysis, is a powerful anti-oxidant with a high potential to neutralize medical toxins. The goal of this study was to demonstrate the beneficial effect of melatonin on epididymal sperm and reproductive parameters in mice treated with acetylsalicylic acid (ASA).
Materials and Methods: Thirty-nine SD rats were randomly split into D1 receptor agonist (chloro-APB), D1 receptor antagonist (SCH23390), and saline groups after preparing NB microinjection model. We observed the effect of NB microinjection of SCH23390, chloro-APB, or saline on the period of induction and recovery time of propofol anesthesia and recorded the changes of electroencephalogram (EEG) simultaneously.
Results: NB microinjection of chloro-APB accelerated the recovery from propofol anesthesia (P<0.05), without affecting the induction of anesthesia (P>0.05); NB microinjection of SCH23390 produced the opposite effects. NB microinjection of saline did not influence the induction or recovery of propofol anesthesia (P>0.05). NB injection of chloro-APB decreased the ratio of δ power and increasedαand β ratios in prefrontal cortex EEG (P<0.05); NB microinjection of SCH23390 increased δ ratio and decreased β ratio (P<0.05); NB microinjection of saline had no significant effect on EEG (P>0.05).
Conclusion: D1 dopamine receptors in NB are involved in modulating the emergence from propofol anesthesia, but not affecting the induction of propofol anesthesia.


1. Vahle-Hinz C, Detsch O, Siemers M, Kochs E. Contributions of GABAergic and glutamatergic mechanisms to isoflurane-induced suppression of thalamic somatosensory information transfer. Exp Brain Res 2007; 176:159-172.
2. Velly LJ, Rey MF, Bruder NJ, Gouvitsos FA, Witjas T, Regis JM, et al. Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia. Anesthesiology 2007; 107:202-212.
3. Fu B, Wang Y, Yang H, Yu T. Effects of etomidate on GABAergic and glutamatergic transmission in rat thalamocortical slices. Neurochem Res 2016; 41:3181-3191.
4. Fu B, Liu C, Zhang Y, Fu X, Zhang L, Yu T. Ketamine attenuates the glutamatergic neurotransmission in the ventral posteromedial nucleus slices of rats. BMC Anesthesiol 2017; 17:111-115.
5. Taylor NE, Chemali JJ, Brown EN, Solt K. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia. Anesthesiology 2013; 118:30-39.
6. Alkire MT, McReynolds JR, Hahn EL, Trivedi AN. Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Anesthesiology 2007; 107:264-272.
7. Zhang Y, Fu B, Liu C, Yu S, Luo T, Zhang L, et al. Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice. FASEB J 2019:fj201802164RR.
8. Luo T, Leung LS. Involvement of tuberomamillary histaminergic neurons in isoflurane anesthesia. Anesthesiology 2011; 115:36-43.
9. Zecharia AY, Nelson LE, Gent TC, Schumacher M, Jurd R, Rudolph U, et al. The involvement of hypothalamic sleep pathways in general anesthesia: testing the hypothesis using the GABAA receptor beta3N265M knock-in mouse. J Neurosci 2009; 29:2177-2187.
10. Leung LS, Luo T, Ma J, Herrick I. Brain areas that influence general anesthesia. Prog Neurobiol 2014; 122:24-44.
11. Leung LS, Petropoulos S, Shen B, Luo T, Herrick I, Rajakumar N, et al. Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics. Exp Neurol 2011; 228:259-269.
12. Pillay S, Vizuete JA, McCallum JB, Hudetz AG. Norepinephrine infusion into nucleus basalis elicits microarousal in desflurane-anesthetized rats. Anesthesiology 2011; 115:733-742.
13. Fu B, Yu T, Yuan J, Gong X, Zhang M. Noradrenergic transmission in the central medial thalamic nucleus modulates the electroencephalographic activity and emergence from propofol anesthesia in rats. J Neurochem 2017; 140:862-873.
14. Franks NP. General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 2008; 9:370-386.
15. Hudetz AG, Vizuete JA, Pillay S. Differential effects of isoflurane on high-frequency and low-frequency gamma oscillations in the cerebral cortex and hippocampus in freely moving rats. Anesthesiology 2011; 114:588-595.
16. Dutta S, Matsumoto Y, Gothgen NU, Ebling WF. Concentration-EEG effect relationship of propofol in rats. J Pharm Sci 1997; 86:37-43.
17. Rudolph U, Antkowiak B. Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 2004; 5:709-720.
18. Campagna JA, Miller KW, Forman SA. Mechanisms of actions of inhaled anesthetics. N Engl J Med 2003; 348:2110-2124.
19. Murphy M, Bruno MA, Riedner BA, Boveroux P, Noirhomme Q, Landsness EC, et al. Propofol anesthesia and sleep: a high-density EEG study. Sleep 2011; 34:283-291A.
20. Alkire MT, Hudetz AG, Tononi G. Consciousness and anesthesia. Science 2008; 322:876-880.
21. Gaykema RP, Zaborszky L. Direct catecholaminergic-cholinergic interactions in the basal forebrain. II. Substantia nigra-ventral tegmental area projections to cholinergic neurons. J Comp Neurol 1996; 374:555-577.
22. Fuller PM, Sherman D, Pedersen NP, Saper CB, Lu J. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 2011; 519:933-956.
23. Xu M, Chung S, Zhang S, Zhong P, Ma C, Chang WC, et al. Basal forebrain circuit for sleep-wake control. Nat Neurosci 2015; 18:1641-1647.
24. Kelz MB, Sun Y, Chen J, Cheng Meng Q, Moore JT, Veasey SC, et al. An essential role for orexins in emergence from general anesthesia. Proc Natl Acad Sci U S A 2008; 105:1309-1314.
25. Zhou X, Wang Y, Zhang C, Wang M, Zhang M, Yu L, et al. The role of dopaminergic VTA neurons in general anesthesia. PLoS One 2015; 10:e0138187.
26. Purdon PL, Sampson A, Pavone KJ, Brown EN. Clinical electroencephalography for anesthesiologists: Part I: background and basic signatures. Anesthesiology 2015; 123:937-960.
27. Solt K, Cotten JF, Cimenser A, Wong KF, Chemali JJ, Brown EN. Methylphenidate actively induces emergence from general anesthesia. Anesthesiology 2011; 115:791-803.
28. Lalley PM. Dopamine1 receptor agonists reverse opioid respiratory network depression, increase CO2 reactivity. Respir Physiol Neurobiol 2004; 139:247-262.