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.