TY - JOUR
T1 - Involvement of reduced acetylcholine release in Δ9-tetrahydrocannabinol-induced impairment of spatial memory in the 8-arm radial maze
AU - Mishima, Kenichi
AU - Egashira, Nobuaki
AU - Matsumoto, Yoshiaki
AU - Iwasaki, Katsunori
AU - Fujiwara, Michihiro
N1 - Funding Information:
Part of this study was supported by a Grant-in Aid for Scientific Research (No. 12771472) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Research Grant (10A–3 and 13A–3) for Nervous and Mental Disorders from the Ministry of Health and Welfare. The authors are grateful to Professor Y. Shoyama, Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyushu University, for his kind supply of natural Δ 9 -tetrahydrocannabinol.
PY - 2002/12/20
Y1 - 2002/12/20
N2 - To clarify the mechanism by which Δ9-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 Δ9-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 Δ9-tetrahydrocannabinol (6 mg/kg, i.p.) in the 8-arm radial maze. Δ9-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 Δ9-tetrahydrocannabinol in the dorsal hippocampus during 60-120 min after the Δ9-tetrahydrocannabinol injection. These findings suggest that inhibition of the cholinergic pathway by reduced acetylcholine release is one of the means by which Δ9-tetrahydrocannabinol impairs spatial memory in the 8-arm radial maze.
AB - To clarify the mechanism by which Δ9-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 Δ9-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 Δ9-tetrahydrocannabinol (6 mg/kg, i.p.) in the 8-arm radial maze. Δ9-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 Δ9-tetrahydrocannabinol in the dorsal hippocampus during 60-120 min after the Δ9-tetrahydrocannabinol injection. These findings suggest that inhibition of the cholinergic pathway by reduced acetylcholine release is one of the means by which Δ9-tetrahydrocannabinol impairs spatial memory in the 8-arm radial maze.
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U2 - 10.1016/S0024-3205(02)02274-9
DO - 10.1016/S0024-3205(02)02274-9
M3 - Article
C2 - 12467880
AN - SCOPUS:0037147072
SN - 0024-3205
VL - 72
SP - 397
EP - 407
JO - Life Sciences
JF - Life Sciences
IS - 4-5
ER -