The serotonin1A receptor agonist 8-OHDPAT reverses delta 9-tetrahydrocannabinol-induced impairment of spatial memory and reduction of acetylcholine release in the dorsal hippocampus in rats.

We studied the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), a 5-HT1A receptor agonist, on both delta9-tetrahydrocannabinol-induced spatial memory impairment in an 8-arm radial maze, and the reduction of acetylcholine release in the dorsal hippocampus as assessed by in vivo microdialysis in rats. A 6 mg/kg i.p. dose of delta9-tetrahydrocannabinol impaired spatial memory in the 8-arm radial maze and decreased the acetylcholine release in the dorsal hippocampus. 8-OHDPAT, at very low doses of 0.1-0.3 microg/kg, reversed both the impairment of spatial memory and the decrease in acetylcholine release induced by delta9-tetrahydrocannabinol. These findings suggest that low doses of 8-OHDPAT may improve delta9-tetrahydrocannabinol-induced impairment of spatial memory by enhancing acetylcholine release in the dorsal hippocampus.