ArticleNeuropharmacology2009
Prolonged exposure to WIN55,212-2 causes downregulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy.
Article in Neuropharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Microglial Cannabinoid CBInternational journal of molecular sciences · 2023Review
- miR-98-5p Prevents Hippocampal Neurons from Oxidative Stress and Apoptosis by Targeting STAT3 in Epilepsy in vitro.Neuropsychiatric disease and treatment · 2023Article
- Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence.Brain sciences · 2022Review
- Commonalities for comorbidity: Overlapping features of the endocannabinoid system in depression and epilepsy.Frontiers in psychiatry · 2022Review
- On the Biomedical Properties of Endocannabinoid Degradation and Reuptake Inhibitors: Pre-clinical and Clinical Evidence.Neurotoxicity research · 2021Review
- The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases.International journal of molecular sciences · 2021Review
- Inhibition of AKT/GSK3β/CREB Pathway Improves the Responsiveness to AMPA Receptor Antagonists by Regulating GRIA1 Surface Expression in Chronic Epilepsy Rats.Biomedicines · 2021Article
- Selective modulation of the cannabinoid type 1 (CBMedChemComm · 2019Review
- Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.Cellular and molecular life sciences : CMLS · 2018Review
- Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures.Metabolic brain disease · 2018Article
- Chemokine CCL2 enhances NMDA receptor-mediated excitatory postsynaptic current in rat hippocampal slices-a potential mechanism for HIV-1-associated neuropathy?Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2016Article
- Mdivi-1 Protects Epileptic Hippocampal Neurons from Apoptosis via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress in Vitro.Neurochemical research · 2016Article
- Cannabinoids and Epilepsy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Review
- Cannabinoid Receptor Type 2 (CB2) Dependent and Independent Effects of WIN55,212-2 on Atherosclerosis in Ldlr-null Mice.Journal of cardiology and therapeutics · 2015Article
- Cannabinoid agonist rescues learning and memory after a traumatic brain injury.Annals of clinical and translational neurology · 2015Article
- Cannabinoids: is there a potential treatment role in epilepsy?Expert opinion on pharmacotherapy · 2015Article
- Seizure activity results in calcium- and mitochondria-independent ROS production via NADPH and xanthine oxidase activation.Cell death & disease · 2014Article
- Disease-modifying effects of RHC80267 and JZL184 in a pilocarpine mouse model of temporal lobe epilepsy.CNS neuroscience & therapeutics · 2014Article
- Seizing an opportunity for the endocannabinoid system.Epilepsy currents · 2014Article
- ABHD6 blockade exerts antiepileptic activity in PTZ-induced seizures and in spontaneous seizures in R6/2 mice.Neuron · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cannabinoids have been shown to cause CB1-receptor-dependent anticonvulsant activity in both in vivo and in vitro models of status epilepticus (SE) and acquired epilepsy (AE). It has been further demonstrated in these models that the endocannabinoid system functions in a tonic manner to suppress seizure discharges through a CB1-receptor-dependent pathway. Although acute cannabinoid treatment has anticonvulsant activity, little is known concerning the effects of prolonged exposure to CB1 agonists and development of tolerance on the epileptic phenotype. This study was carried out to evaluate the effects of prolonged exposure to the CB1 agonist WIN55,212-2 on seizure activity in a hippocampal neuronal culture model of low-Mg(2+) induced spontaneous recurrent epileptiform discharges (SREDs). Following low-Mg(2+) induced SREDs, cultures were returned to maintenance media containing 10, 100 or 1000 nM WIN55,212-2 from 4 to 24 h. Whole-cell current-clamp analysis of WIN55,212-2 treated cultures revealed a concentration-dependent increase in SRED frequency. Immunocytochemical staining revealed that WIN55,212-2 treatment induced a concentration-dependent downregulation of the CB1 receptor in neuronal processes and at both glutamatergic and GABAergic presynaptic terminals. Prolonged exposure to the inactive enantiomer WIN55,212-3 in low-Mg(2+) treated cultures had no effect on the frequency of SREDs or CB1 receptor staining. The results from this study further substantiate a role for a tonic CB1-receptor-dependent endocannabinoid regulation of seizure discharge and suggest that prolonged exposure to cannabinoids results in the development of tolerance to the anticonvulsant effects of cannabinoids and an exacerbation of seizure activity in the epileptic phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.