Abstract

delta 9-Tetrahydrocannabinol (delta 9-THC) induced in both rats and mice an 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, 12 beta-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.(ABSTRACT TRUNCATED AT 250 WORDS)