Involvement of reduced acetylcholine release in Delta9-tetrahydrocannabinol-induced impairment of spatial memory in the 8-arm radial maze.
To clarify the mechanism by which Delta9-tetrahydrocannabinol, a major psychoactive component of marijuana, impairs spatial memory in the 8-arm radial maze in rats via the cholinergic system, we used two acetylcholinesterase inhibitors, physostigmine and tetrahydroaminoacridine. Moreover, we examined the effect of Delta9-tetrahydrocannabinol on acetylcholine release in the frontal cortex and dorsal and ventral hippocampus using in vivo microdialysis. Physostigmine (0.01-0.05 mg/kg, i.p.) and tetrahydroaminoacridine (1-5 mg/kg, p.o.) improved the impairment of spatial memory induced by Delta9-tetrahydrocannabinol (6 mg/kg, i.p.) in the 8-arm radial maze. Delta9-tetrahydrocannabinol (6 mg/kg, i.p.) produced a significant decrease in acetylcholine release in the dorsal hippocampus as assessed by microdialysis. Moreover, tetrahydroaminoacridine at a dose of 1 mg/kg, which improved the impairment of spatial memory, reversed the decrease in acetylcholine release induced by Delta9-tetrahydrocannabinol in the dorsal hippocampus during 60-120 min after the Delta9-tetrahydrocannabinol injection. These findings suggest that inhibition of the cholinergic pathway by reduced acetylcholine release is one of the means by which Delta9-tetrahydrocannabinol impairs spatial memory in the 8-arm radial maze.
Mishima
Kenichi
K
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 814-0180, Fukuoka, Japan.
Egashira
Nobuaki
N
Matsumoto
Yoshiaki
Y
Iwasaki
Katsunori
K
Fujiwara
Michihiro
M
D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology; D013759:Dronabinol / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology; D017551:Microdialysis; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects*; D013619:Tacrine / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D006213:Hallucinogens; D013619:Tacrine; D013759:Dronabinol; D010830:Physostigmine; D000109:Acetylcholine