Scientific Online Resource System

Scripta Scientifica Medica

CB1 ligands modulate learning and memory of OBX rats

Miroslav D. Marinov, Margarita Ivanova, Stiliana Belcheva, Iren Belcheva, Negrin Negrev, Roman Tashev


Purpose. The brain endocannabinoid system has been shown to play a role in learning and memory processes, although the exact mechanisms by which it interferes in these processes are not well established. We aimed at studying the effects of CB1 receptor ligands on learning and memory of rats with an experimental model of depression - olfactory bulbectomy (OBX). Material and methods. Cannabinoid CB1 receptor agonist HU-210 (5 µg) and cannabinoid CB1 receptor antagonist SR 141716A (3 µg) were microinjected i.c.v. in male Wistar rats with olfactory bulbectomy (OBX) model of depression. A passive avoidance task (step through) was used as a test for learning and memory. Results. In the non-OBX group, HU-210 impaired learning and memory processes expressed by the shortened latency time on the retention tests (3 hours and 24 hours after training) and by the decreased percentage of rats that have reached the learning criterion, as compared to the saline-treated controls. SR 141716A did not affect significantly the performance of rats in the step-through task. In the OBX rats HU-210 prolonged the latency time as compared to the saline-treated OBX controls, while SR 141716A did not affect significantly the OBX-related learning and memory deficits. Conclusion. These findings suggest complex modulatory effect of CB1 receptor agonist on learning and memory processes in non-OBX and OBX rats.


learning, memory, CB1 cannabinoid receptors, step through, rat, olfactory bulbectomy

Full Text


Abush H., I. Akirav. Cannabinoids modulate hippocampal memory and plasticity.- Hippocampus, 2010, 20, 1126-1138.

Arenos J. D., R. E. Musty, D. J. Bucci. Blockade of cannabinoid CB1 receptors alters contextual learning and memory.- Eur. J. Pharmacol., 2006, 539, 177-183.

Bures J., W. Buresova. Cortical spreading depression as a memory disturbing factor.- J. Comp. Physiol. Psychol., 1963, 56, 268-272.

Carlson G., Y. Wang, B. E. Alger. Endocannabinoids facilitate the induction of LTP in the hippocampus.- Nat. Neurosci., 2002, 5, 723-724.

Chevaleyre V., P. E. Castillo. Endocannabinoid-mediated metaplasticity in the hippocampus.- Neuron, 2004, 43, 871-881.

Da S., R. N. Takahashi. SR 141716A prevents delta 9-tetrahydrocannabinol-induced spatial learning deficit in a Morris-type water maze in mice.- Prog. Neuropsychopharmacol. Biol. Psychiatry, 2002, 26, 321-325.

Davies S. N., R. G. Pertwee, G. Riedel. Functions of cannabinoid receptors in the hippocampus.- Neuropharmacology, 2002, 42, 993-1007.

De Oliveira Alvares L., B. P. Genro, F. Diehl, J. A. Quillfeldt. Differential role of the hippocampal endocannabinoid system in the memory consolidation and retrieval mechanisms.- Neurobiol. Learn. Mem., 2008, 90, 1-9.

Freund T. F., I. Katona, D. Piomelli. Role of endogenous cannabinoids in synaptic signaling.- Physiol. Rev., 2003, 83, 1017-1066.

Gohier B., L. Ferracci, S. A. Surguladze, E. Lawrence, W. El Hage, M. Z. Kefi et al. Cognitive inhibition and working memory in unipolar depression.- J. Affect. Disord., 2009, 116, 100-105.

Hampson R. E., A. J. Sweatt, A. V. Goonawardena, D. Song, R. H. Chan, V. Z. Marmarelis et al. Memory encoding in hippocampal ensembles is negatively influenced by cannabinoid CB1 receptors.- Behav. Pharmacol., 2011, 22, 335-346.

Hampson R. E., S. A. Deadwyler. Role of cannabinoid receptors in memory storage.- Neurobiol. Dis., 1998, 5, 474-482.

Hernández-Tristán R., C. Arévalo, S. Canals, M. L. Leret. The effects of acute treatment with delta9-THC on exploratory behaviour and memory in the rat.- J. Physiol. Biochem., 2000, 56, 17-24.

Kelly J. P., A. S. Wrynn, B. E. Leonard. The olfactory bulbectomized rat as a model of depression: an update.- Pharmacol. Ther., 1997, 74, 299-316.

Kreitzer A. C., W. G. Regehr. Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells.- Neuron, 2001, 29, 717-727.

Kurtz K. H., J. Pearl. The effects of prior fear experiences on acquired-drive learning.- J. Comp. Physiol. Psychol., 1960, 53, 201-206.

Lichtman A. H. SR 141716A enhances spatial memory as assessed in a radial-arm maze task in rats.- Eur. J. Pharmacol., 2000, 404, 175-179.

Marazziti D., G. Consoli, M. Picchetti, M. Carlini, L. Faravelli. Cognitive impairment in major depression.- Eur. J. Pharmacol., 2010, 626, No 1: 83-86.

Marinov M., M. Ivanova, S. Belcheva, I. Belcheva, R. Tashev. Effects of acutely applied cannabinoid CB1 ligands on learning and memory in rats with a model of depression.- Compt. Rend. Acad. Bulg. Sci., 2013, 6, 1331-1338.

Marsicano G., R. Kuner.- In: Cannabinoids and the Brain. A. Kofalvi, ed. Springer, New York, 2008, 161-202.

Patel S., C. J. Hillard. Role of endocannabinoid signaling in anxiety and depression.- Curr. Top. Behav. Neurosci., 2009, 1, 347-371.

Pazos M. R., E. Núñez, C. Benito, R. M. Tolón, J. Romero. Functional neuroanatomy of the endocannabinoid system.- Pharmacol. Biochem. Behav., 2005, 81, 239-247.

Pellegrino L., A. Cushman. A Stereotaxic Atlas of the Rat Brain. Appleton-Century-Crofts, New York, USA, 1967.

Riedel G., S. N. Davies.- In: Cannabinoids. R. G. Pertwee, ed. Handb. Exp. Pharmacol., Springer-Verlag, Berlin, 168, 2005, 445-477.

Rodríguez-Gaztelumendi A., M. L. Rojo, A. Pazos, A. Díaz. Altered CB receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine.- J. Neurochem., 2009, 108, No 6, 1423-1433.

Song C., B. E. Leonard. The olfactory bulbectomised rat as a model of depression.- Neurosci. Biobehav., Rev., 2005, 29, 627-647.

Takahashi R. N., F. A. Pamplona, M. S. Fernandes. The cannabinoid antagonist SR141716A facilitates memory acquisition and consolidation in the mouse elevated T-maze.- Neurosci. Lett., 2005, 380, 270-275.

Tashev R., M. Ivanova, T. Toromanov, M. Marinov, S. Belcheva, I. Belcheva Olfactory bulbectomy impairs active and passive avoidance learning in rats.- Compt. Rend. Acad. Bulg. Sci., 63, 2010, 617-620.

Varvel S. A., B. F. Cravatt, A. E. Engram, A. H. Lichtman. Fatty acid amide hydrolase

(-/-) mice exhibit an increased sensitivity to the disruptive effects of anandamide or oleamide in a working memory water maze task.- J. Pharmacol. Exp. Ther., 2006, 317, 251-257.

Wilson R. I., R. A. Nicoll. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses.- Nature, 2001, 410, 588-592.



About The Authors

Miroslav D. Marinov
Department of Preclinical and Clinical Sciences Medical University of Varna

Margarita Ivanova
Division of Physiology Medical University of Varna

Stiliana Belcheva
Faculty of Pre-School and Primary School Education, SU "Sv. Kl. Ohridsky" Institute of Neurobiology, Bulgarian Academy of Sciences

Iren Belcheva
Institute of Neurobiology, Bulgarian Academy of Sciences

Negrin Negrev
Medical College - Varna

Roman Tashev
Department of Pathophysiology Medical University of Sofia Institute of Neurobiology, Bulgarian Academy of Sciences

Font Size