Palmitoylethanolamide attenuates PTZ-induced seizures through CB1 and CB2 receptors

Abstract

Epilepsy is one of the most common neurologic disorders. Though there are effective medications available to reduce the symptoms of the disease, their side effects have limited their usage. Palmitoylethanolamide (PEA) has been shown to attenuate seizure in different animal models. The objective of the current study was to evaluate the role of CB1 and CB2 receptors in this attenuation. Male wistar rats were used for the current experiment. PTZ was injected to induce chemical kindling in animals. After verification of kindling in animals, treatment was performed with PEA, AM251 and AM630 in different groups. Latency to induce seizure, seizure stages and latency and duration of fifth stage of seizure was recorded for each animal. Injection of PTZ led to seizure in the animals. Pretreatment with PEA increased the latency to initiate seizures and reduced the duration of seizure. Pretreatment with different dosages of AM251 had contrary effects so that at lower doses they increased the seizure in animals but at higher doses led to the attenuation of seizure. AM630 increased seizures in a dose dependent manner. Combination of the antagonists increased the seizure parameters and attenuated the effect of PEA on seizure. PEA attenuated the PTZ-induced seizures and pretreatment with CB1 and CB2 antagonists diminished this effect of PEA, but still PEA was effective, which might be attributed to the contribution of other receptors in PEA anti-epileptic properties. Findings of the current study implied that endocannabinoid signaling pathway might have an important role in the effects of PEA.

Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection

“…Studies with mixed CB 1 R/CB 2 R agonists (e.g. anandamide, or closely related palmitoylethanolamide) demonstrate primarily anti-convulsive effects in MES- [75,76] and PTZ-induced seizure [77]. Administration of AEA (6.25–50 mg/kg, i.p.)…”

“…Other studies suggest that AM251 has no significant effect on MES seizure when given 15–30 min before testing [59,71], and a pro-convulsive effect in PTZ-induced seizure models at higher doses (5–10 μg, i.c.v.) [77]. …”

Acetaminophen Use for Fever in Children Associated with Autism Spectrum Disorder

“…Administration of PEA has been shown to increase tissue levels of anandamide and increase activation of the endocannabinoid system [ 58 ]. PEA attenuates seizures in rats through CB1 and CB2 cannabinoid receptors [ 59 ]. Antonucci and colleagues in 2015 reported two case studies of boys with ASD in which PEA supplementation reduced inflammatory markers and produced rapid clinically significant improvements.…”

Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy

“…Although the FAAs examined have been reported to activate CB 2 receptors [28][29][30][31], previous publications have also suggested effects on CB 1 receptors [29], PPAR (PPAR-α, -β and -γ) receptors [10,[31][32][33], and TRPV1 [9,34,35] and TRPM8 [36] ion channels. However, a role for CB 2 receptors has been clearly identified in these studies, which utilised highly selective pharmacological tools [26,27], that is consistent with previous studies [6,7].…”