head JofIMAB
Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2022, vol. 28, issue1
Subject Area: Medicine
DOI: 10.5272/jimab.2022281.4202
Published online: 24 January 2022

Original article
J of IMAB. 2022 Jan-Mar;28(1):4202-4206
Margarita Velikova1ORCID logo Corresponding Autoremail, Dobrinka Doncheva1ORCID logo, Roman Tashev2ORCID logo,
1) Department of Physiology and pathophysiology, Medical University - Varna, Bulgaria.
2) Department of Pathophysiology, Medical University - Sofia, Bulgaria.

Dysfunction of the endocannabinoid system has been related to depressive-like behavior. In our study, bilateral olfactory bulbectomy (OBX) was used as an animal model of depression. We evaluated the effect of the selective CB1-antagonist SR-141716A (Rimonabant) on the exploratory and locomotor activity of OBX-rats. Rimonabant was administered intragastrically for 14 days to OBX-rats, divided into 3 experimental groups, where the drug was given before; immediately (1-14 days) after; or 14 days (14-28 day) after OBX. Exploratory and locomotor activity of OBX-rats was tested in an Opto-Varimex apparatus. SR-141716A, administered subchronically, intragastrically exerted locomotor stimulating effects in OBX- and sham-operated rats, while the exploratory activity was not affected. The time interval for the drug administration is of significance for the manifestation of the effects on locomotor activity in OBX-rats. SR-141716A applied 14 days before OBX or after the development of a depressive-like state (14-28 days after OBX), but not immediately after OBX (1-14 days) aggravated the OBX-induced hyperlocomotor state.

Keywords: Cannabinoid receptor, olfactory bulbectomy, exploratory, locomotor, rat,

pdf - Download FULL TEXT /PDF 1412 KB/
Please cite this article as: Velikova M, Doncheva D, Tashev R. CB1-receptor antagonist SR-141716A modulates locomotor activity in OBX-rats. J of IMAB. 2022 Jan-Mar;28(1):4202-4206.
DOI: 10.5272/jimab.2022281.4202

Corresponding AutorCorrespondence to: Assoc. prof. Margarita Velikova, MD, PhD, Department of Physiology and Pathophysiology, Medical University, Varna; 55 M. Drinov Str., 9002 Varna, Bulgaria; E-mail: msvelikova@yahoo.com

1. Busquets-Garcia A, Bains J, Marsicano G. CB1 Receptor Signaling in the Brain: Extracting Specificity from Ubiquity. Neuropsychopharmacology. 2018 Jan;43(1):4-20. [PubMed]
2. Kelly JP, Wrynn AS, Leonard BE. The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther. 1997; 74(3):299-316. [PubMed]
3. Hungund BL, Vinod KY, Kassir SA, Basavarajappa BS, Yalamanchili R, Cooper TB, et al. Upregulation of CB1 receptors and agonist-stimulated [35S] GTPgammaS binding in the prefrontal cortex of depressed suicide victims. Mol Psychiatry. 2004 Feb;9(2):184-90. [PubMed]
4. Koethe D, Llenos IC, Dulay JR, Hoyer C, Torrey EF, Leweke FM, et al. Expression of CB(1) cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression. J Neural Transm (Vienna). 2007; 114(8):1055-63. [PubMed]
5. Rinaldi-Carmona M, Barth F, Heaulme M, Shire D, Calandra B, Congy C, et al. SR141716a, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett. 1994;(350):240–244. [PubMed]
6. Velikova M, Doncheva D, Tashev R. Subchronic effects of ligands of cannabinoid receptors on learning and memory processes of olfactory bulbectomized rats. Acta Neurobiol Exp (Wars). 2020; 80(3):286-296. [PubMed]
7. Velikova M, Doncheva D, Tashev R. Effects of Rimonabant on active avoidance learning in bulbectomized rats. J of IMAB. ;2020 Jan-Mar;26(1):2936-2941. [Crossref]
8. Rodriguez-Gaztelumendi A, Rojo ML, Pazos A, Diaz A. Altered CB receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine. J Neurochem. 2009 Mar;108(6):1423-33. [PubMed]
9. Eisenstein SA, Holmes PV, Hohmann AG. Endocannabinoid modulation of amphetamine sensitization is disrupted in a rodent model of lesion-induced dopamine dysregulation. Synapse.2009 Nov;63(11):941-50. [PubMed]
10. Eisenstein SA, Clapper JR, Holmes PV, Piomelli D, Hohmann AG. A role for 2-arachidonoylglycerol and endocannabinoid signaling in the locomotor response to novelty induced by olfactory bulbectomy. Pharmacol Res. 2010 May;61(5):419-29. [PubMed]
11. Wang XF, Galaj E, Bi GH, Zhang C, He Y, Zhan J, et al. Different receptor mechanisms underlying phytocannabinoid- versus synthetic cannabinoid-induced tetrad effects: Opposite roles of CB1/CB2 versus GPR55 receptors. Br J Pharmacol. 2020 Apr;177(8):1865-1880. [PubMed]
12. Li X, Hempel BJ, Yang HJ, Han X, Bi GH, Gardner EL, et al. Dissecting the role of CB1 ;and CB2 receptors in cannabinoid reward versus aversion using transgenic CB1- and CB2-knockout mice. Eur Neuropsychopharmacol. 2021 Feb;(43):38-51. [PubMed]
13. Antoniou K, Polissidis A, Delis F, Poulia N. The Impact of Cannabinoids on Motor Activity and Neurochemical Correlates. In: In Vivo Neuropharmacology and Neurophysiology. Neuromethods. Philippu A. (eds). Vol. 121. Humana Press, New York, NY. 2017; pp.341-365. [Crossref]
14. Jarbe TU, Di Patrizio NV, Li C, Makriyannis A. The cannabinoid receptor antagonist SR-141716 does not readily antagonize open-field effects induced by the cannabinoid receptor agonist (R)-methanandamide in rats. Pharmacol Biochem Behav. 2003 Jul;75(4):809-21. [PubMed]
15. Bruijnzeel AW, Qi X, Guzhva LV, Wall S, Deng JV, Gold MS, et al. Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats. PLoS One. 2016 Apr 11;11(4):e0153327. [PubMed]
16. Ettaro R, Laudermilk L, Clark SD, Maitra R. Behavioral assessment of rimonabant under acute and chronic conditions. Behav Brain Res. 2020 Jul 15;390:112697. [PubMed]
17. Bass CE, Griffin. G, Grier M , Mahadevan A, Razdan RK, Martin BR. SR-141716A-induced stimulation of locomotor activity. A structure-activity relationship study. Pharmacol Biochem Behav 2002 Dec;74(1):31-40.  [PubMed]
18. Valverde O, Torrens M. CB1 receptor-deficient mice as a model for depression Neurosci. 2012 Mar 1;204:193-206. [PubMed]
19. Mahesh R, Sharma P, Gautam BK, Bhatt S, Pandey DK. Antidepressant-like activity of cannabinoid type-1 receptor antagonist, Rimonabant: behavioural investigation in animal model of depression. Int J Pharma Bio Sci. 2010 Jan-Mar;1(1):35.. [Crossref]
20. Lee S, Kim DH, Yoon SH, Ryu JH. Sub-chronic administration of Rimonabant causes loss of antidepressive activity and decreases doublecortin immunoreactivity in the mouse hippocampus. Neurosci Lett. 2009 Dec 25;467(2):111-6. [PubMed].

Received: 30 December 2021
Published online: 24 January 2022

back to Online Journal