Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure.
Susana Mato, David Robbe, Nagore Puente, Pedro Grandes, Olivier J. J. Manzoni
Journal of Neuroscience December 14, 2005 DOI: 10.1523/jneurosci.2294-05.2005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Delta9-tetrahydrocannabinol (THC) |
| Duration | 1 week of repeated in vivo THC treatment |
| Topics | Cannabis Depression |
| Key findings | Repeated in vivo THC treatment in mice reduced CB1 receptor coupling to G(i/o) proteins and CB1R-mediated inhibition of excitatory transmission at cortico-accumbens synapses, yet long-term depression remained normal because a presynaptic mGluR2/3-dependent mechanism reversibly replaced the impaired endocannabinoid system. The authors propose this as a novel form of presynaptic homeostasis. |
Abstract
Alterations of long-term synaptic plasticity have been proposed to participate in the development of addiction. To preserve synaptic functions, homeostatic processes must be engaged after exposure to abused drugs. At the mouse cortico-accumbens synapses, a single in vivo injection of Delta9-tetrahydrocannabinol (THC) suppresses endocannabinoid-mediated long-term depression. Using biochemical and electrophysiological approaches, we now report that 1 week of repeated in vivo THC treatment reduces the coupling efficiency of cannabinoid CB1 receptors (CB1Rs) to G(i/o) transduction proteins, as well as CB1R-mediated inhibition of excitatory synaptic transmission at the excitatory synapses between the prefrontal cortex and the nucleus accumbens (NAc). Nonetheless, we found that cortico-accumbens synapses unexpectedly express normal long-term depression because of a reversible switch in its underlying mechanisms. The present data show that, in THC-treated mice, long-term depression is expressed because a presynaptic mGluR2/3 (metabotropic glutamate receptor 2/3)-dependent mechanism replaces the impaired endocannabinoid system. Thus, in the NAc, a novel form of presynaptic homeostasis rescues synaptic plasticity from THC-induced deficits.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 11
- Prenatal cannabinoid exposure alters excitation-inhibition balance through glutamate and GABA receptor-mediated signaling. Journal of Biological Chemistry July 2026
- Δ9 -Tetrahydrocannabinol self-administration induces cell type-specific adaptations in the nucleus accumbens core. Addiction Biology August 2023
- The loss of NMDAR-dependent LTD following cannabinoid self-administration is restored by positive allosteric modulation of CB1 receptors. Addiction Biology November 2020
- Cannabinoid modulation of drug reward and the implications of marijuana legalization. Brain Research December 2, 2015
- Neuroimaging studies of acute effects of THC and CBD in humans and animals: a systematic review. Current Pharmaceutical Design 2014
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