Riluzole blocks HU210-facilitated ventral tegmental long-term depression by enhancing glutamate uptake in astrocytes.
Zhiqiang Liu, Yi Xu, Xiaofan Zhang, Jinfeng Miao, Jing Han, Zhou Zhu
Neuroscience Letters June 21, 2019 DOI: 10.1016/j.neulet.2019.04.021 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Cultured astrocytes and 2-month-old rats |
| Interventions | Riluzole HU210 |
| Topics | Depression |
| Keywords | Astrocyte Glutamate transporter-1 Hu210 Long-term depression Riluzole |
| Key findings | Riluzole inhibited HU210-induced glutamate release by increasing GLT-1 expression in cultured astrocytes, and infusion of riluzole into the bilateral VTA of rats prevented HU210-facilitated LTD induction in 2-month-old animals; this prevention was blocked by the selective GLT-1 inhibitor dihydrokainate. The authors propose these results may offer insights into new therapeutic approaches for cannabis addiction. |
Abstract
The lifetime prevalence of addiction to cannabis (marijuana or cannabinoids) is among the highest of that of all illicit drugs in developed countries, and no effective treatment for cannabis addiction is currently available. Previous studies in our research group suggested that astrocyte-mediated long-term depression (LTD) in ventral tegmental area (VTA) dopamine neurons plays a pivotal role in the development of cannabis addiction. The present study was designed to investigate the effects and potential mechanisms of riluzole, a drug used for the treatment of motor neuron diseases, on cannabinoid-facilitated LTD induction. We demonstrated that riluzole significantly inhibited HU210-induced glutamate release through increased expression of glial glutamate transporter-1 (GLT-1) in cultured astrocytes, and an infusion of riluzole into the bilateral VTA in rats prevented the potent cannabinoid HU210-facilitated LTD induction in 2-month-old animals, which was blocked by bath application of dihydrokainate (DHK), a selective GLT-1 inhibitor. Our results show the effects and potential mechanism of action of riluzole in cannabinoid-facilitated LTD induction, which may provide insights into new therapeutic approaches for cannabis addiction.
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| Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress | 2017 | Preclinical animal study |