Reduced expression of glutamate receptors and phosphorylation of CREB are responsible for in vivo Delta9-THC exposure-impaired hippocampal synaptic plasticity.
Ni Fan, Hongwei Yang, Jian Zhang, Chu Chen
Journal of Neurochemistry February 2010 DOI: 10.1111/j.1471-4159.2009.06489.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Basic experimental animal study Peer reviewed |
|---|---|
| Population | Mice (hippocampal tissue) |
| Intervention | Delta9-THC |
| Duration | 7 consecutive days of in vivo exposure |
| Topics | Cannabis Neuroplasticity |
| Key findings | Repeated in vivo Delta9-THC exposure for 7 days impaired hippocampal LTP, an effect prevented by CB1R inhibition or deletion. THC also reduced hippocampal GluR1, NR2A, and NR2B expression, AMPA/NMDA current ratios, and CREB phosphorylation in a CB1R-dependent manner. The authors propose these molecular changes may underlie THC-induced impairment of long-term synaptic plasticity. |
Abstract
Chronic use of marijuana impairs synaptic plasticity and cognitive function. However, the molecular mechanisms by which marijuana alters long-term synaptic plasticity are largely unknown. Here, we show that repeated in vivo exposures to Delta9-THC for 7 consecutive days significantly impaired hippocampal long-term potentiation (LTP) of excitatory glutamatergic synaptic transmission. The Delta9-THC exposure-induced decrease in LTP was prevented by pharmacological inhibition or deletion of the cannabinoid 1 receptor (CB1R). To determine the molecular mechanisms underlying Delta9-THC-altered LTP, we targeted expression and function of the glutamate receptors (GluR) and phosphorylation status of cAMP-response element-binding protein (CREB). Chronic in vivo exposure to Delta9-THC produced CB1R-dependent decreases in expression of hippocampal GluR1, NR2A, and NR2B, the ratio of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/NMDA receptor-gated currents, and phosphorylation of CREB. Our results suggest that reduced expression and function of the GluR subunits and phosphorylation of CREB may underlie the impaired long-term synaptic plasticity induced by repeated in vivo exposure to Delta9-THC.
Comparable studies
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Citations in the library
Cited by 11
- Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Journal of Psychopharmacology October 5, 2012
- Effects of Cannabis on Glutamatergic Neurotransmission: The Interplay between Cannabinoids and Glutamate. Cells June 29, 2024
- Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice. British Journal of Pharmacology July 13, 2023
- Impairment of Synaptic Plasticity by Cannabis, Δ9-THC, and Synthetic Cannabinoids. Cold Spring Harbor perspectives in medicine May 3, 2021
- [Dependence and Cytotoxicity of Components of Cannabis]. Yakugaku Zasshi 2020
and 6 more in the library
Cites 8
- Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation. Learning & Memory 2007
- Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure. Journal of Neuroscience December 14, 2005
- Role of lipids and lipid signaling in the development of cannabinoid tolerance. Life Sciences August 19, 2005
- Marijuana and cannabinoid regulation of brain reward circuits. British Journal of Pharmacology September 2004
- Functional tolerance and blockade of long-term depression at synapses in the nucleus accumbens after chronic cannabinoid exposure. Journal of Neuroscience June 15, 2003
and 3 more in the library