Cannabinoid antagonist SLV326 induces convulsive seizures and changes in the interictal EEG in rats

Perescis, M.F.J.; Bruin, Natasja de; Heijink, Liesbeth; Kruse, Chris G.; Vinogradova, Lyudmila V.; Lüttjohann, Annika; Luijtelaar, Gilles van; Rijn, Clementina M. van

doi:10.1371/journal.pone.0165363

Cited by 8 publications

(3 citation statements)

References 54 publications

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“…Examples of peripheral CB 2 R agonists are listed in Table 8 below. Regarding the use of CB 1 R antagonists [136], of note is that side effects of CB 1 R antagonism may include neuropsychiatric sequalae (e.g., anhedonia and anxiety), pain, hyperalgesia, hypertension, and pro-convulsive effects [136,371]. Examples of CB 1 R antagonists are listed in Table 9 below.…”

Section: Gat228 (R-enantiomer)mentioning

confidence: 99%

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

Lowe

Toyang²,

Steele

et al. 2021

IJMS

160

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The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.

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Section: Gat228 (R-enantiomer)mentioning

confidence: 99%

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

Lowe

Toyang²,

Steele

et al. 2021

IJMS

160

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“…The seizures analyzed in the present study occur during chronic treatment with the CB1 antagonist SLV326, as it was reported previously in [26]. Since the method to elicit the seizures was reported extensively there, here it will be repeated only in short.…”

Section: Subjects and Local Field Potential Recordingmentioning

confidence: 85%

Directional functional coupling during limbic seizures in rats revealed by nonlinear Granger causality

Sysoev¹,

Perescis²,

Vinogradova³

et al. 2018

Russ Open Med J

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Subject and Purpose -Temporal lobe epilepsy is increasingly recognized to involve widespread network alterations. In this study the temporal dynamics of directional interactions between the frontal cortex, hippocampus, thalamus and midbrain during limbic seizures are analyzed in rats. Methods -Local field potentials were recorded in Wistar rats expressing generalized limbic seizures, Racine's stage 4-5. These spontaneous seizures occur during chronic treatment with a CB1 (cannabinoid receptor type 1) antagonist SLV326. Time-frequency analysis, time-varying adapted nonlinear Granger causality and mutual information were applied. The Granger causality and mutual information values estimated from seizure episodes were compared to those of seizure-free periods. Results -During the seizure, two stages were detected: a high frequency (15-20 Hz) stage followed by a low frequency (2 Hz) stage. At seizure onset, a drop in coupling between all recorded sites was found. After the seizure onset, coupling restored to normal levels in the midbrain -hippocampus pair, but remained reduced in all other studied channel pairs for at least 10 s after the onset. The transition between stages and the seizure termination were characterized by couplings increase in some pairs and by decrease in others. Conclusion -Spontaneous generalized limbic seizures can be considered as a result of pathological reorganization of coupling architecture between different brain structures, developing in time, and providing transitions between seizure stages. These findings bring together views, considering seizures as an increase of couplings in the brain, and hypotheses, regarding seizures rather as a decoupled state. Cite as Sysoev IV, Perescis MFJ, Vinogradova LV, Sysoeva MV, van Rijn CM. Directional functional coupling during limbic seizures in rats revealed by nonlinear Granger causality. Russian Open Medical Journal 2018; 7: e0404.Correspondence to Ilya V. Sysoev. Work address: Astrakhanskaya str.,

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“…Conversely, CB 1 antagonists, such as rimonabant, induce spontaneous convulsive seizures [25][26][27] or increase the occurrence of existing seizures in several in vitro [28] and in vivo [29][30][31] epilepsy or seizure models. There is also evidence in humans: partial seizures were observed in a patient treated with rimonabant for obesity, who had a history of idiopathic generalized epilepsy [32].…”

Section: Introductionmentioning

confidence: 99%

Altered SWD stopping mechanism in WAG/Rij rats subchronically treated with the cannabinoid agonist R(+)WIN55,212-2

Perescis

Flipsen

Luijtelaar

et al. 2020

Epilepsy & Behavior

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A single injection of the cannabinoid agonist R(+)WIN55,212-2 (WIN) is known to cause an increase of the mean duration of spontaneously occurring spike-and-wave discharges (SWDs) in rats of the WAG/Rij strain, a genetic model for absence epilepsy. The aim of the present study was to establish whether repeated activation of CB 1 receptors with WIN leads to tolerance in its effect on SWD parameters, spectral density, and behavior over time. Adult male WAG/Rij rats (n = 16) were treated with WIN (6 mg/kg) or vehicle (olive oil). Injections (s.c.) took place 3 times per week during 2 weeks. Electroencephalogram (EEG) recordings, each lasting 24 h, were made 3 times: immediately before the first injection (baseline), immediately after the first injection (acute treatment), and after 2 weeks of treatment (subchronic treatment). The recordings were analyzed regarding incidence, durations of SWDs, and hazard rates of the durations of SWDs, the latter to describe SWD stopping probabilities. Putative changes in the spectral content of the EEG before and after WIN during active and passive behaviors were additionally investigated. Spike-and-wave discharge incidence was not affected by the acute and subchronic treatments. The mean duration of the SWDs was significantly longer than controls in the acute WIN-treated animals [11.9-s standard error of the mean (SEM): 0.64 compared with 8.4-s SEM: 0.25] as well as in subchronically treated animals (11.5-s SEM: 1.00 compared with 8.4-s SEM: 0.25). Hazard rates were significantly lower for WIN-treated animals at SWD durations in the 5.04-20.16-s range on both occasions. No effects of WIN on the frequency spectrum of the ongoing EEG were found, neither acutely nor after repeated administration. Evidence for tolerance was not found. The results on the mean duration and hazard rates suggest that stimulating the endocannabinoid system affects the SWD stopping mechanism, resulting in more long SWDs. We speculate that this effect is likely to be a direct result of CB 1 receptor agonism and a subsequent decrease in the availability of gamma-aminobutyric acid (GABA) in the reticular thalamic nucleus, which further weakens, in WAG/Rij rats already disturbed, the stopping mechanism of the SWDs.

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Cannabinoid antagonist SLV326 induces convulsive seizures and changes in the interictal EEG in rats

Cited by 8 publications

References 54 publications

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

Directional functional coupling during limbic seizures in rats revealed by nonlinear Granger causality

Altered SWD stopping mechanism in WAG/Rij rats subchronically treated with the cannabinoid agonist R(+)WIN55,212-2

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