Journal article
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain
Pain (Amsterdam), Vol.160(1), pp.136-150
01/2019
Handle:
https://hdl.handle.net/2376/106164
PMID: 30157131
Abstract
Low dose of cannabidiol ameliorates mechanical allodynia and anxious behavior and restores impaired serotonergic transmission in a neuropathic pain model in rats.
Clinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis that interacts with the serotonin (5-HT)
1A
receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact on models of neuropathic pain are unknown. First, using in vivo single-unit extracellular recordings in rats, we demonstrated that acute intravenous (i.v.) increasing doses of CBD (0.1-1.0 mg/kg) decreased the firing rate of 5-HT neurons in the dorsal raphe nucleus, which was prevented by administration of the 5-HT
1A
antagonist WAY 100635 (0.3 mg/kg, i.v.) and the TRPV
1
antagonist capsazepine (1 mg/kg, i.v.) but not by the CB
1
receptor antagonist AM 251 (1 mg/kg, i.v.). Repeated treatment with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) increased 5-HT firing through desensitization of 5-HT
1A
receptors. Rats subjected to the spared nerve injury model for 24 days showed decreased 5-HT firing activity, mechanical allodynia, and increased anxiety-like behavior in the elevated plus maze test, open-field test, and novelty-suppressed feeding test. Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Antiallodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), whereas the anxiolytic effect was blocked only by WAY. Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV
1
activation, reduces anxiety through 5-HT
1A
receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
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Details
- Title
- Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain
- Creators
- Danilo De Gregorio - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QCRyan J McLaughlin - Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WALuca Posa - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QCRafael Ochoa-Sanchez - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QCJustine Enns - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QCMartha Lopez-Canul - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QCMatthew Aboud - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QCSabatino Maione - Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Università degli Studi della Campania “Luigi Vanvitelli,” NaplesStefano Comai - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QCGabriella Gobbi - Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QC
- Publication Details
- Pain (Amsterdam), Vol.160(1), pp.136-150
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Wolters Kluwer; Philadelphia, PA
- Identifiers
- 99900546504801842
- Language
- English
- Resource Type
- Journal article