Salvinorin A Does Not Affect Seizure Threshold in Mice

Salvinorin A, a potent plant-derived hallucinogen that selectively activates the κ-opioid receptor, did not alter seizure thresholds in mice across three acute seizure tests. At doses of 0.1–10 mg/kg injected intraperitoneally, it had no significant effect on the thresholds for myoclonic twitch, generalized clonic seizure, forelimb tonus, tonic hindlimb extension, or psychomotor seizures. It also did not impair motor coordination or muscular strength. This preliminary report suggests that salvinorin A does not influence seizure susceptibility in these models, though further research is needed.

Study at a glance

Abstract

The κ-opioid receptor has recently gained attention as a new molecular target in the treatment of many psychiatric and neurological disorders including epilepsy. Salvinorin A is a potent plant-derived hallucinogen that acts as a highly selective κ-opioid receptor agonist. It has unique structure and pharmacological properties, but its influence on seizure susceptibility has not been studied so far. Therefore, the aim of the present study was to investigate the effect of salvinorin A on seizure thresholds in three acute seizure tests in mice. We also examined its effect on muscular strength and motor coordination. The obtained results showed that salvinorin A (0.1–10 mg/kg, i.p.) did not significantly affect the thresholds for the first myoclonic twitch, generalized clonic seizure, or forelimb tonus in the intravenous pentylenetetrazole seizure threshold test in mice. Likewise, it failed to affect the thresholds for tonic hindlimb extension and psychomotor seizures in the maximal electroshock- and 6 Hz-induced seizure threshold tests, respectively. Moreover, no changes in motor coordination (assessed in the chimney test) or muscular strength (assessed in the grip-strength test) were observed. This is a preliminary report only, and further studies are warranted to better characterize the effects of salvinorin A on seizure and epilepsy.