Cannabinoid CB(1) receptor agonists increase rat cortical and hippocampal acetylcholine release in vivo.
Intravenous administration of the cannabinoid CB(1) receptor agonists (R-(+)-[2, 3-Dihydro-5-methyl-3[morpholinyl)methyl]-pyrrolo[1,2,3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate), WIN 55,212-2 (10, 37.5, 75 and 150 microg/kg), and ((6aR)-trans-3-(1, 1-Dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6, 6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol), HU 210 (1 and 4 microg/kg) dose-dependently increased acetylcholine release in dialysates from the prefrontal cortex and the hippocampus of freely moving rats. Administration of the cannabinoid receptor antagonist [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide]HCl, SR 141716A, at a dose that per se did not affect basal acetylcholine release (2. 5 microg/kg), prevented the increase of acetylcholine release by WIN 55,212-2 (150 microg/kg i.v.) or by HU 210 (4 microg/kg i.v.) in both areas. These data demonstrate that, at low i.v. doses, the synthetic cannabinoid CB(1) receptor agonists, WIN 55,212-2 and HU 210 stimulate cortical and hippocampal acetylcholine release.
Department of Toxicology, University of Cagliari and Centre for Neuropharmacology, CNR, V.le A. Diaz, 182, 09126, Cagliari, Italy.
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Acquas
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Pisanu
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Marrocu
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Di Chiara
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors; D000077285:Rimonabant
D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol; D000109:Acetylcholine; C062018:HU 211; D000077285:Rimonabant