Inhibition of hippocampal acetylcholine release after acute and repeated Delta9-tetrahydrocannabinol in rats.

The effects of acute and repeated administration of Delta9-tetrahydrocannabinol (Delta9-THC), the psychoactive principle of marijuana, on acetylcholine release in the hippocampus was studied in freely moving rats by microdialysis. The acute intraperitoneal (i.p.) administration of Delta9-THC at the doses of 2.5 and 5 mg/kg reduced acetylcholine release by about 25% and 45%, respectively. A dose of 7.5 mg/kg produced no further reduction. Delta9-THC effects were antagonized by the cannabinoid CB1 antagonist SR141716A at the i.p. dose of 1 mg/kg, per se ineffective in modifying acetylcholine concentrations. After a repeated exposure (twice daily for up to seven days) to Delta9-THC (7.5 mg/kg, i.p.) or vehicle (0.3 ml/kg, i.p.), the inhibitory effect of Delta9-THC (2.5 and 5 mg/kg, i.p) on acetylcholine release was not reduced. The results confirm previous observations that cannabinoids inhibit acetylcholine release through cannabinoid CB1 receptors, and indicate that no tolerance to this effects develops after a repeated Delta9-THC administration.