title: Coadministration of cannabinoid CB1-receptor and adenosine A1-receptor antagonists improves the acquisition of spatial memory in mice:  participation of glutamatergic neurotransmission.
abstract: The aim of this study was to characterize the interaction of adenosine A1-receptor and cannabinoid CB1-receptor antagonists in the water maze and object-location tasks, and to evaluate the participation of glutamatergic neurotransmission in the hippocampus in the learning enhancement induced by the coadministration of both antagonists. Our results show that coadministration of ineffective doses of DPCPX (8-cyclopentyl-1,3-dipropylxanthine) (an A1-receptor antagonist) and AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) (a CB1-receptor antagonist) in different proportions enhanced the acquisition of spatial learning. N-methyl-D-aspartate receptor blockade disrupted the effects of the selected drug combination [AM251 0.25 mg/kg intraperitoneally (i.p.)+DPCPX 0.30 mg/kg i.p.] either in the water maze or in the object-location task. Moreover, this drug combination induced a significant ex-vivo enhancement in glutamate release into hippocampal slices. In addition, the blockade of N-methyl-D-aspartate receptors with MK-801 (0.25 µg/site) infused into the hippocampal CA1 area reversed the effects of coadministration, as evaluated in the object-location task. In conclusion, this is the first study to show that A1-receptor and CB1-receptor antagonists might interact on hippocampal neurons to enhance spatial memory in mice.
authors.affiliation: Departments of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Fabrício Luiz
authors.initials: FL
authors.lastname: Assini
authors.forename: Carina Akemi
authors.initials: CA
authors.lastname: Nakamura
authors.forename: Tetsade Camboim
authors.initials: TC
authors.lastname: Piermartiri
authors.forename: Carla Inês
authors.initials: CI
authors.lastname: Tasca
authors.forename: Reinaldo Naoto
authors.initials: RN
authors.lastname: Takahashi
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D013037:Spatial Behavior / Q000187:drug effects*; D009435:Synaptic Transmission; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014970:Xanthines; C103505:AM 251; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C051360:1,3-dipropyl-8-cyclopentylxanthine