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.
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Guy M. Everett Laboratory of Neuropsychopharmacology, Department of Neuroscience 'Bernard B. Brodie', University of Cagliari, Via Porcell 4, 09124, Cagliari, Italy.
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002186:Cannabinoids / Q000037:antagonists & inhibitors; D003071:Cognition / Q000187:drug effects; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism; D000077285:Rimonabant
D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C052413:delta(9-11)-tetrahydrocannabinol; D013759:Dronabinol; D000109:Acetylcholine; D000077285:Rimonabant