Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.

Autor: Roebuck AJ; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada.; School of Liberal Arts, Yukon University, Whitehorse, YT, Canada., Greba Q; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Onofrychuk TJ; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., McElroy DL; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Sandini TM; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada., Zagzoog A; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada., Simone J; Department of Biological Sciences, Centre for Neuroscience, Brock University, St. Catharines, ON, Canada., Cain SM; Michael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British Colombia, Vancouver, BC, Canada., Snutch TP; Michael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British Colombia, Vancouver, BC, Canada., Laprairie RB; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.; Department of Pharmacology, College of Medicine, Dalhousie University, Halifax, NS, Canada., Howland JG; Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2022 Feb; Vol. 55 (4), pp. 1063-1078. Date of Electronic Publication: 2021 Jan 23.
DOI: 10.1111/ejn.15096
Abstrakt: There is significant interest in the use of cannabinoids for the treatment of many epilepsies including absence epilepsy (AE). Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model many aspects of AE including the presence of spike-and-wave discharges (SWDs) on electroencephalogram (EEG) and behavioral comorbidities, such as elevated anxiety. However, the effects of cannabis plant-based phytocannabinoids have not been tested in GAERS. Therefore, we investigated how SWDs in GAERS are altered by the two most common phytocannabinoids, Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), and exposure to smoke from two different chemovars of cannabis. Animals were implanted with bipolar electrodes in the somatosensory cortex and EEGs were recorded for 2 hr. Injected THC (1-10 mg/kg, i.p.) dose-dependently increased SWDs to over 200% of baseline. In contrast, CBD (30-100 mg/kg, i.p.) produced a ~50% reduction in SWDs. Exposure to smoke from a commercially available chemovar of high-THC cannabis (Mohawk, Aphria Inc.) increased SWDs whereas a low-THC/high-CBD chemovar of cannabis (Treasure Island, Aphria Inc.) did not significantly affect SWDs in GAERS. Pre-treatment with a CB1R antagonist (SR141716A) did not prevent the high-THC cannabis smoke from increasing SWDs, suggesting that the THC-mediated increase may not be CB1R-dependent. Plasma concentrations of THC and CBD were similar to previously reported values following injection and smoke exposure. Compared to injected CBD, it appears Treasure Island did not increase plasma levels sufficiently to observe an anti-epileptic effect. Together these experiments provide initial evidence that acute phytocannabinoid administration exerts the biphasic modulation of SWDs and may differentially impact patients with AE.
(© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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