Effects of cannabinoids on levels of acetylcholine and choline and on turnover rate of acetylcholine in various regions of the mouse brain
Tripathi, H.L.; Vocci, F.J.; Brase, D.A.; Dewey, W.L.
Alcohol and Drug Research 7(5-6): 525-532
1987
ISSN/ISBN: 0883-1386 PMID: 3620017 Document Number: 298855
The psychoactive cannabinoids, .DELTA.9-tetrahydrocannabinol (.DELTA.9-THC), .DELTA.8-tetrahydrocannabinol (.DELTA.8-THC), 11-hydroxy-.DELTA.9-tetrahydrocannabinol (11-OH-.DELTA.9-THC) and 9-nor-9.beta.-hydroxyhexahydrocannabinol (.beta.-HHC), as well as the nonpsychoactive cannabinoids, cannabinol (CBN), cannabidiol (CBD), abnormal CBD, .DELTA.8-THC methyl ether (1-OCH3-.DELTA.8-THC) and 9-nor-9.alpha.-hydroxyhexahydrocannabinol (.alpha.-HHC), were used to assess the role of cholinergic mechanisms in the different behavioral actions of these cannabinoids. Their effects on mouse brain choline and acetylcholine (ACh) levels and on ACh turnover were determined in cortex, hippocampus, striatum, midbrain and medulla-pons. .DELTA.9-THC (30 mg/kg) caused a significant elevation of ACh in all five brain areas. 11-OH-.DELTA.9-THC(30 mg/kg) increased ACh in hippocampus, striatum and midbrain. .DELTA.8-THC (30 mg/kg) increased ACh in cortex and hippocampus. .DELTA.9-THC and 11-OH-.DELTA.9-THC increased choline in midbrain and cortex, whereas .beta.-HHC increased choline in all areas, except hippocampus, at a dose of 30 mg/kg. Also at this dose, .DELTA.9-THC, 11-OH-.DELTA.9-THC, .DELTA.8-THC and .beta.-HHC decreased ACh (100 mg/kg) and .alpha.-HHC (100 mg/kg). ACh turnover was also decreased in midbrain by 1-OCH3-.DELTA.8-THC and in the stratium by .alpha.-HHC. Thus, the most consistent effects of cannabinoids, both psychotomimetic and nonpsychotomimetic, were to increase ACh and decrease ACh turnover in the hippocampus. It is concluded that cannabinoid effects on cholinergic mechanisms appear to be more closely related to the CNS depression than to psychotomimetic activity.