Reduction of hippocampal acetylcholine turnover in rats treated with (-)-delta 8-tetrahydrocannabinol and its 1',2'-dimethyl-heptyl homolog.

The effects of (-)-delta 8-tetrahydrocannabinol (THC), (+)-delta 8-THC, and the dimethyl-heptyl (DMH) homolog of (-)-delta 8-THC (delta 8-THC-DMH) have been compared with the action of (-)-delta 9-THC on the turnover rate of acetylcholine in various brain areas. The data demonstrate that (-)-delta 8-THC-DMH, (-)-delta 9-THC and (-)- delta 8-THC all specifically reduce ther turnover rate of acetylcholine in the hippocampus in a dose-dependent manner ((-)-delta 8-THC-DMH > (-)-delta 9-THC > (-)-delta 8-THC) without altering the acetylcholine or choline content (except for high doses of (-)-delta 8-THC-DMH). The (+)-isomer of delta 8-THC fails to change any cholinergic parameter. The selectivity of action suggests that the tetrahydrocannabinoids may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septal-hippocampal pathway.