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Interactions between the nitrergic and the endocannabinoid system in rats exposed to the elevated T-maze

Published online by Cambridge University Press:  05 April 2021

Luara Augusta Batista Open the ORCID record for Luara Augusta Batista [Opens in a new window] ,
Fabricio de Araújo Moreira  and
Daniele Cristina de Aguiar
Luara Augusta Batista*
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Fabricio de Araújo Moreira
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Daniele Cristina de Aguiar
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
*
Author for correspondence: Luara Augusta Batista, Email: [email protected]
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Abstract

Objective:

The aim of this study was to test the hypothesis that synthesis of nitric oxide (NO) and activation of CB1 receptors have opposite effects in a behavioural animal model of panic and anxiety.

Methods:

To test the hypothesis, male Wistar rats were exposed to the elevated T-maze (ETM) model under the following treatments: L-Arginine (L-Arg) was administered before treatment with WIN55,212-2, a CB1 receptor agonist; AM251, a CB1 antagonist, was administered before treatment with L-Arg. All treatments were by intraperitoneal route.

Results:

The CB1 receptor agonist, WIN55,212-2 (1 mg/kg), induced an anxiolytic-like effect, which was prevented by pretreatment with an ineffective dose of L-Arg (1 mg/kg). Administration of AM251 (1 mg/kg), a CB1 antagonist before treatment with L-Arg (1 mg/kg) did not produce anxiogenic-like responses.

Conclusion:

Altogether, this study suggests that the anxiolytic-like effect of cannabinoids may occur through modulation of NO signalling.

Keywords

nitric oxideCB1 receptorspanicanxietycannabinoids
Type
Short Communication
Information
Acta Neuropsychiatrica , Volume 33 , Issue 4 , August 2021 , pp. 206 - 210
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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References

Aguiar, DC, Hott, SC, Deolindo, MV, Guimaraes, FS and Resstel, LB (2014) The dorsolateral periaqueductal grey N-methyl-D-aspartate/nitric oxide/cyclic guanosine monophosphate pathway modulates the expression of contextual fear conditioning in rats. Journal of Psychopharmacology 28, 479–485.CrossRefGoogle ScholarPubMed
Anand, R, Gulati, K and Ray, A (2012) Pharmacological evidence for the role of nitric oxide in the modulation of stress-induced anxiety by morphine in rats. European Journal of Pharmacology 676, 71–74.CrossRefGoogle ScholarPubMed
Batista, LA, Bastos, JR and Moreira, FA (2015) Role of endocannabinoid signalling in the dorsolateral periaqueductal grey in the modulation of distinct panic-like responses. Journal of Psychopharmacology 29, 335–343.CrossRefGoogle ScholarPubMed
Batista, LA, Gobira, PH, Viana, TG, Aguiar, DC and Moreira, FA (2014) Inhibition of endocannabinoid neuronal uptake and hydrolysis as strategies for developing anxiolytic drugs. Behavioral Pharmacology 25, 425–433.CrossRefGoogle ScholarPubMed
Bredt, DS and Snyder, SH (1992) Nitric oxide, a novel neuronal messenger. Neuron 8, 3–11.CrossRefGoogle ScholarPubMed
Calixto, AV, Vandresen, N, De Nucci, G, Moreno, H and Faria, MS (2001) Nitric oxide may underlie learned fear in the elevated T-maze. Brain Research Bulletin 55, 37–42.CrossRefGoogle ScholarPubMed
File, SE, Lippa, AS, Beer, B and Lippa, MT (2004) Animal tests of anxiety. Current Protocols in Neuroscience 8, 3.Google ScholarPubMed
Gobira, PH, Aguiar, DC and Moreira, FA (2013) Effects of compounds that interfere with the endocannabinoid system on behaviors predictive of anxiolytic and panicolytic activities in the elevated T-maze. Pharmacology Biochemistry and Behaviour 110, 33–39.CrossRefGoogle ScholarPubMed
Graeff, FG, Netto, CF and Zangrossi, H Jr (1998) The elevated T-maze as an experimental model of anxiety. Neuroscience Biobehavioral Reviews 23, 237–246.CrossRefGoogle ScholarPubMed
Griebel, G and Holmes, A (2013) 50 years of hurdles and hope in anxiolytic drug discovery. Nature Review Drug Discovery 12, 667–687.CrossRefGoogle ScholarPubMed
Guimaraes, FS, Beijamini, V, Moreira, FA, Aguiar, DC and De Lucca, AC (2005) Role of nitric oxide in brain regions related to defensive reactions. Neuroscience Biobehavioral Reviews 29, 1313–1322.CrossRefGoogle ScholarPubMed
Hillard, CJ, Muthian, S and Kearn, CS (1999) Effects of CB(1) cannabinoid receptor activation on cerebellar granule cell nitric oxide synthase activity. FEBS Letters 459, 277–281.CrossRefGoogle ScholarPubMed
Jesse, CR, Bortolatto, CF, Savegnago, L, Rocha, JB and Nogueira, CW (2008) Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Progress in Neuropsychopharmacology & Biology Psychiatry 32, 1838–1843.CrossRefGoogle ScholarPubMed
Joshi, JC, Ray, A and Gulati, K (2015) Effects of morphine on stress induced anxiety in rats: role of nitric oxide and Hsp70. Physiology and Behavior 139, 393–396.CrossRefGoogle ScholarPubMed
Katona, I and Freund, TF (2012) Multiple functions of endocannabinoid signaling in the brain. Annual Review of Neuroscience 35, 529–558.CrossRefGoogle Scholar
Kim, SH, Won, SJ, Mao, XO, Ledent, C, Jin, K and Greenberg, DA (2006) Role for neuronal nitric-oxide synthase in cannabinoid-induced neurogenesis. Journal of Pharmacology Experimental Therapeutics 319, 150–154.CrossRefGoogle ScholarPubMed
Lipina, C and Hundal, HS (2017) The endocannabinoid system: ‘NO’ longer anonymous in the control of nitrergic signalling? Journal of Molecular Cell Biology 9, 91–103.CrossRefGoogle ScholarPubMed
Lisboa, SF, Camargo, LH, Magesto, AC, Resstel, LB and Guimaraes, FS (2014) Cannabinoid modulation of predator fear: involvement of the dorsolateral periaqueductal gray. International Journal of Neuropsychopharmacology 17, 1193–1206.CrossRefGoogle ScholarPubMed
Lisboa, SF, Gomes, FV, Silva, AL, Uliana, DL, Camargo, LH, Guimaraes, FS, Cunha, FQ, Joca, SR and Resstel, LB (2015) Increased contextual fear conditioning in iNOS knockout mice: additional evidence for the involvement of nitric oxide in stress-related disorders and contribution of the endocannabinoid system. International Journal of Neuropsychopharmacology 18, pyv005.CrossRefGoogle ScholarPubMed
Lisboa, SF, Magesto, AC, Aguiar, JC, Resstel, LB and Guimaraes, FS (2013) Complex interaction between anandamide and the nitrergic system in the dorsolateral periaqueductal gray to modulate anxiety-like behavior in rats. Neuropharmacology 75, 86–94.CrossRefGoogle ScholarPubMed
Masood, A, Banerjee, B, Vijayan, VK and Ray, A (2003) Modulation of stress-induced neurobehavioral changes by nitric oxide in rats. European Journal of Pharmacology 458, 135–139.CrossRefGoogle ScholarPubMed
Moncada, S and Higgs, A (1993) The L-arginine-nitric oxide pathway. New England Journal of Medicine 329, 2002–2012.Google ScholarPubMed
Riebe, CJ and Wotjak, CT (2011) Endocannabinoids and stress. Stress 14, 384–397.CrossRefGoogle ScholarPubMed
Vincent, SR (2010) Nitric oxide neurons and neurotransmission. Progress in Neurobiology 90, 246–255.CrossRefGoogle ScholarPubMed
Volke, V, Soosaar, A, Koks, S, Vasar, E and Mannisto, PT (1998) L-Arginine abolishes the anxiolytic-like effect of diazepam in the elevated plus-maze test in rats. European Journal of Pharmacology 351, 287–290.CrossRefGoogle ScholarPubMed
Zangrossi, H Jr. and Graeff, FG (2014) Serotonin in anxiety and panic: contributions of the elevated T-maze. Neuroscience Biobehavioral Reviews 46, 397–406.CrossRefGoogle ScholarPubMed
Zhang, J, Huang, XY, Ye, ML, Luo, CX, Wu, HY, Hu, Y, Zhou, QG, Wu, DL, Zhu, LJ and Zhu, DY (2010) Neuronal nitric oxide synthase alteration accounts for the role of 5-HT1A receptor in modulating anxiety-related behaviors. Journal of Neuroscience 30, 2433–2441.CrossRefGoogle ScholarPubMed