Pharmacological characterization of cannabinoids in the elevated plus maze
Onaivi, E.S.; Green, M.R.; Martin, B.R.
Journal of Pharmacology and Experimental Therapeutics 253(3): 1002-1009
1990
ISSN/ISBN: 0022-3565 PMID: 2162942 Document Number: 356527
.DELTA.9-Tetrahydrocannabinol (.DELTA.9-THC) induced on both rats and mice and increased aversion to the open arms of the elevated plus maze which was similar to that produced by anxiogenic agents. This effect of .DELTA.9-THC was approximately three times greater in rats than in mice. When the behavioral effects of the cannabinoids were characterized further in the mouse, it was found that .DELTA.9-11-THC, 12beta-NH2-.DELTA.8-THC, levonantradol and (-)-11-OH-.DELTA.8-THC-DMH produced effects that were similar to those of .DELTA.9-THC. The effect was found to be enantioselective in that (+)-11-OH-.DELTA.8-THC-DMH was inactive even at a dose 200 times greater than an active dose of (-)-11-OH-.DELTA.8-THC-DMH. In contrast to the effects of .DELTA.9-THC, mice treated with cannabidiol and nabilone spent a greater amount of time in the open arm of the maze, an effect similar to that produced by diazepam, the reference anxiolytic agent. In this test situation, 11-nor-.DELTA.8-THC-9-carboxylic acid and abnormal cannabidiol did not alter the behavior of the animals at doses up to 20 and 100 mg/kg, respectively. Pretreatment with either the bidirectional inverse agonist carboline-3-carboxylate or diazepam (at doses that did not modify normal behavior on the elevated plus maze) blocked the effect of .DELTA.9-THC. In addition, 11-nor-.DELTA.8-THC-9-carboxylic acid, at doses that did not alter the behavioral response of mice, was also effective at blocking the effect of .DELTA.9-THC as well as those of cannabidiol and nabilone. Pretreatment with naloxone was ineffective in blocking the effects of any of these cannabinoids. Furthermore, flumazenil, a high affinity ligand for the benzodiazepine receptor that lacks intrinsic activity, was effective not only at blocking the effects of .DELTA.9-THC but also the effects of cannabidiol and nabilone. The mechanism for these cannabinoid behavioral effects remains unclear but may involve the GABA/benzodiazepine supramolecular complex.