Involvement of reduced acetylcholine release in Delta9-tetrahydrocannabinol-induced impairment of spatial memory in the 8-arm radial maze.
Kenichi Mishima, Nobuaki Egashira, Yoshiaki Matsumoto, Katsunori Iwasaki, Michihiro Fujiwara
Life Sciences December 20, 2002 DOI: 10.1016/s0024-3205(02)02274-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Delta9-tetrahydrocannabinol physostigmine tetrahydroaminoacridine |
| Dose | Delta9-tetrahydrocannabinol 6 mg/kg i.p.; physostigmine 0.01-0.05 mg/kg i.p.; tetrahydroaminoacridine 1-5 mg/kg p.o. |
| Measures | 8-arm radial maze, in vivo microdialysis |
| Topics | Cannabis |
| Key findings | Delta9-tetrahydrocannabinol (6 mg/kg, i.p.) impaired spatial memory in the 8-arm radial maze and decreased acetylcholine release in the dorsal hippocampus of rats. Physostigmine and tetrahydroaminoacridine improved the memory impairment, and tetrahydroaminoacridine (1 mg/kg) reversed the decrease in dorsal hippocampal acetylcholine release. The authors suggest that reduced acetylcholine release, inhibiting the cholinergic pathway, is one mechanism by which Delta9-tetrahydrocannabinol impairs spatial memory. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 5
- Prefrontal cortical distribution of muscarinic M2 and cannabinoid-1 (CB1) receptors in adult male mice with or without chronic adolescent exposure to Δ9-tetrahydrocannabinol. Cerebral Cortex November 21, 2022
- Neuroimaging studies of acute effects of THC and CBD in humans and animals: a systematic review. Current Pharmaceutical Design 2014
- Involvement of opioid system in cognitive deficits induced by ∆⁹-tetrahydrocannabinol in rats. Psychopharmacology February 2012
- Effects of Endocannabinoid System Modulation on Cognitive and Emotional Behavior Frontiers in Behavioral Neuroscience July 22, 2011
- [Neuropsychopharmacology of delta-9-tetrahydrocannabinol]. Annales pharmaceutiques francaises August 2008
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