Effects of cannabinoids on levels of acetylcholine and choline and on turnover rate of acetylcholine in various regions of the mouse brain.

Abstract

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 turnover in the hippocampus, as did CBN (10-30 mg/kg), 1-OCH3-delta 8-THC (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 striatum 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.(ABSTRACT TRUNCATED AT 250 WORDS)