α-Spinasterol, a TRPV1 receptor antagonist, elevates the seizure threshold in three acute seizure tests in mice.

Katarzyna Socała,Mateusz Pieróg,Piotr Wlaź,Dorota Nieoczym

doi:10.1007/s00702-015-1391-7

Katarzyna Socała, Mateusz Pieróg + Show 2 more

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https://doi.org/10.1007/s00702-015-1391-7

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Abstract

α-Spinasterol is a plant-derived compound which was reported to act as a selective antagonist for the transient receptor potential vanilloid 1 (TRPV1) receptor. Several studies revealed that the TRPV1 receptors might modulate seizure activity in animal models of seizures and epilepsy. The aim of the present study was to investigate the effect of α-spinasterol on the seizure threshold in three acute models of seizures, i.e., in the intravenous (i.v.) pentylenetetrazole (PTZ) seizure test, in the maximal electroshock seizure threshold (MEST) test and in the model of psychomotor seizures induced by 6 Hz stimulation in mice. Our results revealed significant anticonvulsant effect of α-spinasterol in all the used seizure tests. In the i.v. PTZ test, statistically significant elevation was noted in case of the threshold for myoclonic twitches (doses of 0.1–1 mg/kg) and generalized clonus seizures (doses of 0.5 and 1 mg/kg) but not for tonic seizures. The studied TRPV1 antagonist also increased the threshold for tonic hindlimb extension in the MEST (doses of 0.5 and 1 mg/kg) and 6 Hz psychomotor seizure (doses of 0.1 and 0.5 mg/kg) tests in mice. Furthermore, α-spinasterol did not produce any significant impairment of motor coordination (assessed in the chimney test) and muscular strength (investigated in the grip-strength test) and it did not provoke significant changes in body temperature in mice. Based on the results of our study and the fact that α-spinasterol is characterized by good blood–brain permeability, we postulate further investigation of this compound to precisely evaluate mechanism of its anticonvulsant action and opportunity of its usage in clinical practice.

Highlights

The transient receptor potential vanilloid 1 receptor (TRPV1), first identified in 1997 as a capsaicin receptor (Caterina et al 1997), is a non-selective cation channel composed of six transmembrane domains with a short cation-permeable pore region (Pingle et al 2007; Vriens et al 2009)
The aim of the present study was to investigate the effect of a-spinasterol on the seizure threshold in three acute models of seizures, i.e., in the intravenous (i.v.) pentylenetetrazole (PTZ) seizure test, in the maximal electroshock seizure threshold (MEST) test and in the model of psychomotor seizures induced by 6 Hz stimulation in mice
The effect of a-spinasterol on the threshold for the first myoclonic twitch is shown in Fig. 1a [one-way ANOVA: F(4,63) = 13.560, p \ 0.0001]. a-Spinasterol at a dose of 0.1 mg/kg slightly raised the threshold for the first myoclonic twitch (p \ 0.05 vs. the vehicle-treated group)

Summary

Introduction

The transient receptor potential vanilloid 1 receptor (TRPV1), first identified in 1997 as a capsaicin receptor (Caterina et al 1997), is a non-selective cation channel composed of six transmembrane domains with a short cation-permeable pore region (Pingle et al 2007; Vriens et al 2009). The TRPV1 receptors are predominantly expressed in peripheral sensory neurons, in nociceptive Ad and C fibres, where they play a crucial role in temperature sensing and noxious stimuli detection (Szallasi et al 2007; Vriens et al 2009). Numerous studies showed their importance in mediating various pain conditions, especially inflammatory thermal hyperalgesia and chronic pain. The TRPV1 receptors in the brain are likely activated by endogenous agonists (Martins et al 2014). Several studies showed that the TRPV1 receptors may be implicated in the neurobiology of addictive behavior, anxiety, mood disorders, cognition and emotion (Manna and Umathe 2012a; Martins et al 2014)

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