title: The Influence of the CB1 Receptor Ligands on the Schizophrenia-Like Effects in Mice Induced by MK-801.
abstract: A growing body of psychiatric research has emerged, focusing on the role of endocannabinoid system in psychiatric disorders. For example, the endocannabinoid system, via cannabinoid CB (CB1 and CB2) receptors, is able to control the function of many receptors, such as N-methyl-D-aspartate (NMDA) receptors connected strictly with psychosis or other schizophrenia-associated symptoms. The aim of the present research was to investigate the impact of the CB1 receptor ligands on the symptoms typical for schizophrenia. We provoked psychosis-like effects in mice by an acute administration of NMDA receptor antagonist, MK-801 (0.1-0.6 mg/kg). An acute administration of MK-801 induced psychotic symptoms, manifested in the increase in locomotor activity (hyperactivity), measured in actimeters, as well as the memory impairment, assessed in the passive avoidance task. We revealed that an acute injection of CB1 receptor agonist, oleamide (5-20 mg/kg), had no influence on the short- and long-term memory-related disturbances, as well as on the hyperlocomotion in mice, provoking by an acute MK-801. In turn, an amnestic effects or hyperactivity induced by an acute MK-801 was attenuated by an acute administration of AM 251 (0.25-3 mg/kg), a CB1 receptor antagonist. The present findings confirm that endocannabinoid system is able to modify a variety of schizophrenia-like responses, including the cognitive disturbances and hyperlocomotion in mice. Antipsychotic-like effects induced by CB1 receptor antagonist, obtained in our research, confirm the potential effect of CB1 receptor blockade and could have important therapeutic implications on clinical settings, in the future.
authors: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a Street, 20-093, Lublin, Poland. marta.kruk@umlub.pl.
authors: Marta
authors: M
authors: Kruk-Slomka
authors: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a Street, 20-093, Lublin, Poland.
authors: Barbara
authors: B
authors: Budzynska
authors: Department of Mathematics and Medical Biostatistics, Medical University of Lublin, Jaczewskiego 4 Street, 20-954, Lublin, Poland.
authors: Tomasz
authors: T
authors: Slomka
authors: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a Street, 20-093, Lublin, Poland.
authors: Izabela
authors: I
authors: Banaszkiewicz
authors: Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a Street, 20-093, Lublin, Poland.
authors: Grazyna
authors: G
authors: Biala
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009829:Oleic Acids / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*; D012565:Schizophrenic Psychology
chemical_list: D014150:Antipsychotic Agents; C578453:CNR1 protein, mouse; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; D009829:Oleic Acids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D016291:Dizocilpine Maleate; C029407:oleylamide
keywords: CB1 receptor ligands; Endocannabinoid system; Mice; NMDA receptor antagonist; Schizophrenia