Cannabinoids enhance N-methyl-D-aspartate-induced excitation of locus coeruleus neurons by CB1 receptors in rat brain slices.
We studied the effect of cannabinoids on the activity of N-methyl-d-aspartate (NMDA) receptors in the locus coeruleus from rat brain slices by single-unit extracellular recordings. As expected, NMDA (100 microM) strongly excited (by nine fold) the cell firing activity of the locus coeruleus. Perfusion with the endocannabinoid anandamide (1 and 10 microM) or the anandamide transport inhibitor AM 404 (30 microM) enhanced the NMDA-induced excitation of locus coeruleus neurons. Similarly, the synthetic agonists R(+)-WIN 55212-2 (10 microM) and CP 55940 (30 microM) enhanced the effect of NMDA. In the presence of the CB(1) receptor antagonists SR 141716A (1 microM) or AM 251 (1 microM), the enhancement induced by anandamide (10 microM) was blocked. Our results suggest that cannabinoids modulate the activity of NMDA receptors in the locus coeruleus through CB(1) receptors.
Mendiguren
Aitziber
A
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, E-48940 Leioa, Bizkaia, Spain.
Pineda
Joseba
J
D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D004347:Drug Interactions; D004594:Electrophysiology; D063388:Endocannabinoids; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077285:Rimonabant
D000700:Analgesics; D001095:Arachidonic Acids; D048588:Benzoxazines; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D018690:Excitatory Amino Acid Agonists; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D016202:N-Methylaspartate; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide