Nitrous Oxide-induced Impairment of Spatial Working Memory Requires Activation of GABAergic Pathways

Author(s): Dimitris E. Emmanouil*, Evan D. Klein, Katherine Chen, Abigail L. Brewer, Yangmiao Zhang, Raymond M. Quock

Journal Name: Current Psychopharmacology

Volume 9 , Issue 1 , 2020

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Abstract:

Background: Previous research from our laboratory implicated opioid and benzodiazepine- GABA mechanisms in other effects of N2O (antinociception and anxiolysis), so a decision was made to study these as potential mechanisms of N2O-induced dysfunction of spatial working memory.

Objective: to explore potential mechanisms of N2O in reducing spatial working memory in mice.

Methods: we monitored spontaneous alternation behavior (SAB) in male NIH Swiss mice exposed to N2O during a T-maze spontaneous alternation task (T-SAT).

Results: mice that were exposed to 70% N2O (in O2) exhibited severely and significantly reduced spontaneous alternation behavior in the T-SAT. Mice in this environment alternated their route only 33% of the time, in comparison to the control (room air) rate of alternation at approximately 70%. Mice pretreated with the benzodiazepine antagonist, flumazenil exhibited a dose-dependent restoration of spatial working memory under 70% N2O in the T-SAT. Alternatively, pretreatment with neither the GABAA antagonist gabazine nor the opioid antagonist naloxone had any appreciable effect on the N2O-reduced SAB.

Conclusion: this study verified that 70% N2O can reduce spatial working memory in mice, which appears to involve benzodiazepine mechanisms in the brain.

Keywords: Amnesia, flumazenil, gabazine, mouse, naloxone, nitrous oxide, spatial memory.

[1]
Eckenhoff JE. Relationship of anesthesia to postoperative personality changes in children. Am J Dis Child 1953; 86: 587-91.
[2]
Kain ZN, Mayes LC, O’Connor TZ, Cicchetti DV. Preoperative anxiety in children. Predictors and outcomes. Arch Pediatr Adolesc Med 1996; 150(12): 1238-45.
[http://dx.doi.org/10.1001/archpedi.1996.02170370016002] [PMID: 8953995]
[3]
File SE, Easton P, Skelly AM. Amnesia for dental procedures and mood change following treatment with nitrous oxide or midazolam. Int Clin Psychopharmacol 1991; 6(3): 169-78.
[http://dx.doi.org/10.1097/00004850-199100630-00005] [PMID: 1806623]
[4]
Culley DJ, Raghavan SV, Waly M, et al. Nitrous oxide decreases cortical methionine synthase transiently but produces lasting memory impairment in aged rats. Anesth Analg 2007; 105(1): 83-8.
[http://dx.doi.org/10.1213/01.ane.0000266491.53318.20] [PMID: 17578961]
[5]
van Amsterdam J, Nabben T, van den Brink W. Recreational nitrous oxide use: Prevalence and risks. Regul Toxicol Pharmacol 2015; 73(3): 790-6.
[http://dx.doi.org/10.1016/j.yrtph.2015.10.017] [PMID: 26496821]
[6]
Sarter M, Bodewitz G, Stephens DN. Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist beta-carbolines. Psychopharmacology (Berl) 1988; 94(4): 491-5.
[http://dx.doi.org/10.1007/BF00212843] [PMID: 2836875]
[7]
Isseroff A. Limited recovery of spontaneous alternation after extensive hippocampal damage: evidence for a memory impairment. Exp Neurol 1979; 64(2): 284-94.
[http://dx.doi.org/10.1016/0014-4886(79)90269-3] [PMID: 428506]
[8]
Olton DS, Samuelson RJ. Remembrance of places passed: spatial memory in rats. J Exp Psychol Anim Behav Process 1976; 2: 97-116.
[http://dx.doi.org/10.1037/0097-7403.2.2.97]
[9]
Emmanouil DE, Quock RM. Advances in understanding the actions of nitrous oxide. Anesth Prog 2007; 54(1): 9-18.
[http://dx.doi.org/10.2344/0003-3006(2007)54[9:AIUTAO]2.0.CO;2] [PMID: 17352529]
[10]
Berkowitz BA, Ngai SH, Finck AD. Nitrous oxide “analgesia”: resemblance to opiate action. Science 1976; 194(4268): 967-8.
[http://dx.doi.org/10.1126/science.982058] [PMID: 982058]
[11]
Berkowitz BA, Finck AD, Ngai SH. Nitrous oxide analgesia: reversal by naloxone and development of tolerance. J Pharmacol Exp Ther 1977; 203(3): 539-47.
[PMID: 925957]
[12]
Quock RM, Graczak LM. Influence of narcotic antagonist drugs upon nitrous oxide analgesia in mice. Brain Res 1988; 440(1): 35-41.
[http://dx.doi.org/10.1016/0006-8993(88)91156-0] [PMID: 2833991]
[13]
Zelinski LM, Ohgami Y, Quock RM. Exposure to nitrous oxide stimulates a nitric oxide-dependent neuronal release of β-endorphin in ventricular-cisternally-perfused rats. Brain Res 2009; 1300: 37-40.
[http://dx.doi.org/10.1016/j.brainres.2009.08.091] [PMID: 19747467]
[14]
Ohgami Y, Chung E, Quock RM. Nitrous oxide-induced NO-dependent neuronal release of β-endorphin from the rat arcuate nucleus and periaqueductal gray. Brain Res 2010; 1366: 38-43.
[http://dx.doi.org/10.1016/j.brainres.2010.10.010] [PMID: 20937263]
[15]
Quock RM, Emmanouil DE, Vaughn LK, Pruhs RJ. Benzodiazepine receptor mediation of behavioral effects of nitrous oxide in mice. Psychopharmacology (Berl) 1992; 107(2-3): 310-4.
[http://dx.doi.org/10.1007/BF02245153] [PMID: 1319602]
[16]
Czech DA, Quock RM. Nitrous oxide induces an anxiolytic-like effect in the conditioned defensive burying paradigm, which can be reversed with a benzodiazepine receptor blocker. Psychopharmacology (Berl) 1993; 113(2): 211-6.
[http://dx.doi.org/10.1007/BF02245699] [PMID: 7855183]
[17]
Quock RM, Wetzel PJ, Maillefer RH, Hodges BL, Curtis BA, Czech DA. Benzodiazepine receptor-mediated behavioral effects of nitrous oxide in the rat social interaction test. Pharmacol Biochem Behav 1993; 46(1): 161-5.
[http://dx.doi.org/10.1016/0091-3057(93)90335-Q] [PMID: 8255907]
[18]
Quock RM, Curtis BA, Reynolds BJ, Mueller JL. Dose-dependent antagonism and potentiation of nitrous oxide antinociception by naloxone in mice. J Pharmacol Exp Ther 1993; 267(1): 117-22.
[PMID: 8229738]
[19]
Emmanouil DE, Johnson CH, Quock RM. Nitrous oxide anxiolytic effect in mice in the elevated plus maze: mediation by benzodiazepine receptors. Psychopharmacology (Berl) 1994; 115(1-2): 167-72.
[http://dx.doi.org/10.1007/BF02244768] [PMID: 7862891]
[20]
Li S, Quock RM. Comparison of N2O- and chlordiazepoxide-induced behaviors in the light/dark exploration test. Pharmacol Biochem Behav 2001; 68(4): 789-96.
[http://dx.doi.org/10.1016/S0091-3057(01)00487-7] [PMID: 11526978]
[21]
The Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, DC: National Academies Press 2010.
[22]
Hughes RN. The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. Neurosci Biobehav Rev 2004; 28(5): 497-505.
[http://dx.doi.org/10.1016/j.neubiorev.2004.06.006] [PMID: 15465137]
[23]
Gerlai R. A new continuous alternation task in T-maze detects hippocampal dysfunction in mice. A strain comparison and lesion study. Behav Brain Res 1998; 95(1): 91-101.
[http://dx.doi.org/10.1016/S0166-4328(97)00214-3] [PMID: 9754881]
[24]
Spowart-Manning L, van der Staay FJ. The T-maze continuous alternation task for assessing the effects of putative cognition enhancers in the mouse. Behav Brain Res 2004; 151(1-2): 37-46.
[http://dx.doi.org/10.1016/j.bbr.2003.08.004] [PMID: 15084419]
[25]
Deacon RMJ, Rawlins JNP. T-maze alternation in the rodent. Nat Protoc 2006; 1(1): 7-12.
[http://dx.doi.org/10.1038/nprot.2006.2] [PMID: 17406205]
[26]
Richman CL, Dember WN, Kim P. Spontaneous alternation behavior: A Review. New York: Springer 1989.
[27]
Robson JG, Burns BD, Welt PJ. The effect of inhaling dilute nitrous oxide upon recent memory and time estimation. Can Anaesth Soc J 1960; 7: 399-410.
[http://dx.doi.org/10.1007/BF03021298] [PMID: 13742373]
[28]
Ramsay DS, Leonesio RJ, Whitney CW, Jones BC, Samson HH, Weinstein P. Paradoxical effects of nitrous oxide on human memory. Psychopharmacology (Berl) 1992; 106(3): 370-4.
[http://dx.doi.org/10.1007/BF02245420] [PMID: 1570385]
[29]
Thompson JM, Neave N, Moss MC, Scholey AB, Wesnes K, Girdler NM. Cognitive properties of sedation agents: comparison of the effects of nitrous oxide and midazolam on memory and mood. Br Dent J 1999; 187(10): 557-62.
[http://dx.doi.org/10.1038/sj.bdj.4800330] [PMID: 10630045]
[30]
Fowler B, White PL, Wright GR, Ackles KN. Narcotic effects of nitrous oxide and compressed air on memory and auditory perception. Undersea Biomed Res 1980; 7(1): 35-46.
[PMID: 7385446]
[31]
Rabat A, Hardouin J, Courtière A. Nitrous oxide impairs selective stages of working memory in rats. Neurosci Lett 2004; 364(1): 22-6.
[http://dx.doi.org/10.1016/j.neulet.2004.03.083] [PMID: 15193748]
[32]
Culley DJ, Baxter M, Yukhananov R, Crosby G. The memory effects of general anesthesia persist for weeks in young and aged rats. Anesth Analg 2003; 96(4): 1004-9.
[http://dx.doi.org/10.1213/01.ANE.0000052712.67573.12] [PMID: 12651650]
[33]
Culley DJ, Baxter MG, Yukhananov R, Crosby G. Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology 2004; 100(2): 309-14.
[http://dx.doi.org/10.1097/00000542-200402000-00020] [PMID: 14739805]
[34]
Dember WN, Fowler H. Spontaneous alternation behavior. Psychol Bull 1958; 55(6): 412-28.
[http://dx.doi.org/10.1037/h0045446] [PMID: 13602020]
[35]
Dember WN, Fowler H. Spontaneous alteration after free and forced trials. Can J Psychol 1959; 13: 151-4.
[http://dx.doi.org/10.1037/h0083776] [PMID: 13815794]
[36]
Rosenegger D, Parvez K, Lukowiak K. Enhancing memory formation by altering protein phosphorylation balance. Neurobiol Learn Mem 2008; 90(3): 544-52.
[http://dx.doi.org/10.1016/j.nlm.2008.06.005] [PMID: 18625329]
[37]
Wilson S. A survey of the American Academy of Pediatric Dentistry membership: nitrous oxide and sedation. Pediatr Dent 1996; 18(4): 287-93.
[PMID: 8857656]
[38]
Hynes MD, Berkowitz BA. Nitrous oxide stimulation of locomotor activity: evidence for an opiate-like behavioral effect. J Pharmacol Exp Ther 1979; 209(2): 304-8.
[PMID: 439005]
[39]
Hynes MD, Berkowitz BA. Catecholamine mechanisms in the stimulation of mouse locomotor activity by nitrous oxide and morphine. Eur J Pharmacol 1983; 90(1): 109-14.
[http://dx.doi.org/10.1016/0014-2999(83)90220-0] [PMID: 6873171]
[40]
Orii R, Ohashi Y, Halder S, Giombini M, Maze M, Fujinaga M. GABAergic interneurons at supraspinal and spinal levels differentially modulate the antinociceptive effect of nitrous oxide in Fischer rats. Anesthesiology 2003; 98(5): 1223-30.
[http://dx.doi.org/10.1097/00000542-200305000-00026] [PMID: 12717145]
[41]
Abraini JH, Kriem B, Balon N, Rostain JC, Risso JJ. Gamma-aminobutyric acid neuropharmacological investigations on narcosis produced by nitrogen, argon, or nitrous oxide. Anesth Analg 2003; 96(3): 746-9.
[http://dx.doi.org/10.1213/01.ANE.0000050282.14291.38] [PMID: 12598256]


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VOLUME: 9
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Year: 2020
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DOI: 10.2174/2211556009666200217121518
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