Olfactory bulbectomy (OBX) is an experimental model of depression, which has recently been used as a model of Alzheimer's disease due to the development of neurodegenerative changes in the brain. The OBX model in rodents is accompanied by biochemical, morphological and structural changes in the brain, as well as by many behavioral changes. A common finding in the OBX model are memory deficits, which are present in both depressive disorders and neurodegenerative diseases. There is evidence that the memory-impairing effect of cannabinoids is associated with activation of the cannabinoid CB1 receptors in the brain. The aim of the present study was to investigate the effects of the CB1 antagonist Rimonabant (SR 141716A) administered intragastrically daily for 14 days on the memory processes of OBX rats, tested in a passive avoidance (PA) paradigm. Rimonabant was administered to OBX rats, divided into three experimental groups: before OBX; immediately after OBX (1-14 days); with the presence of a depressive-like state (14-28 days after OBX). Rimonabant showed a tendency to improve the learning and memory of sham-operated controls, whereas no significant change in the behavioral responses was observed upon administration 14 days before OBX. However, Rimonabant, administered immediately after OBX completely prevented the development of memory deficit in a PA test, while its administration 14-28 days after OBX ameliorated the memory disturbances induced by bulbectomy.
The results indicate that the CB1 antagonist Rimonabant may ameliorate the development of a memory deficit in OBX rats.
Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science 2002; 296: 678-682.
Pertwee RG, Howlett AC, Abood ME, Alexander SP, DiMarzo V, Elphick MR et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands:beyond CB1and CB2. Pharmacol.Rev 2010; 62: 588-631.
Maccarrone M, Dainese E, Oddi S. Intracellular trafficking of anandamide: new concepts for signaling. Trends Biochem.Sci 2010; 35: 601-608.
Busquets-Garcia A, Bains J, Marsicano G. CB1 Receptor Signaling in the Brain: Extracting Specificity from Ubiquity. Neuropsychopharmacology 2018; 43: 4-20.
Silvestri C, DiMarzo V. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Cell Metab. 2013; 17: 475- 490.
Cabral GA, Griffin-Thomas L. Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev.Mol.Med. 2009; 11:e3.
Song C, Leonard BE. The olfactory bulbectomised rat as a model of depression.
Neurosci. Biobehav. Rev. 2005; 29: 627-647.
Bures J, Buresova W. Cortical spreading depression as a memory-disturbing factor. J. Comp. Physiol. Psychol. 1963; 56: 268-272.
Kruk-Slomka M, Dzik A, Budzynska B, Biala G. Endocannabinoid System: the Direct and Indirect Involvement in the Memory and Learning Processes-a Short Review. Mol. Neurobiol. 2017; 54: 8332-8347.
Rinaldi-Carmona M, Barth F, Heaulme M, Alonso R, Shire D, Congy C, Soubrie P, Breliere JC et al. Biochemical and pharmacological characterization of SR141716A, the first potent and selective brain cannabinoid receptor antagonist. Life Sci 1995; 56(23-24): 1941-1947.
Terranova JP, Storme JJ, Lafon N, PéÅ•io A, Rinaldi-Carmona M, Le Fur G, Soubrié P. Improvement ofmemory in rodents by the selective CB1 cannabinoid receptor antagonist, SR 141716. Psychopharmacology 1996; 126(2): 165-172.
Takahashi RN, Pamplona FA, Fernandes MS. The cannabinoid antagonist SR141716A facilitates memory acquisition and consolidation in the mouse elevated T-maze. Neurosci Lett 2005; 380 (3): 270-275.
Wolff MC, Leander JD. SR141716A, a cannabinoid CB1 receptor antagonist, improves memory in a delayed radial maze task. Eur J Pharmacol 2003; 477(3): 213-217.
Abush H, Akirav I. Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory. Neuropsychopharmacology 2013; 38(8):1521-1534
Yehuda S, Rabinovitz S. (2014) Olfactory bulbectomy as a putative model for Alzheimer: The protective role of essential fatty acids. PharmaNutrition 2: 12-14.
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; 61(5): 419-429.
Wise LE, Iredale PA, Stokes RJ, Lichtman AH. Combination of rimonabant and donepezil prolongs spatial memory duration. Neuropsychopharmacology. 2007; 32(8):1805-1812.
