Behavioral studies of the abuse potential and anesthetic and sedative effects of etomidate in male rodents.

Rationale: Etomidate is a short-acting general anesthetic for clinical use and has been used as alternative to propofol or added to the powdered drug and e-cigarette cartridges recently, leading to an increase in abuse. But there have been no studies conducted on the abuse potential of etomidate.

Objectives and methods: This study aimed to evaluate the abuse potential of etomidate via conditioned place preference (CPP) and self-administration tests, reflecting its rewarding and reinforcing effects. In addition, righting reflex and open-field tests were conducted to evaluate the anesthetic and sedative effects of etomidate.

Results: In male mice, the ED₅₀ after intraperitoneal (i.p.) injection of anesthetic effect for etomidate was 9.156 mg/kg and the ED₅₀ of the sedative effect 5 min after intraperitoneal injection was 2.389 mg/kg. Etomidate induced CPP in male mice at the minimum dose of 3 mg/kg i.p. and supported stable self-administration in male rats at the dose of 0.075 mg/kg/intravenous infusion. The dose-response curve of etomidate was an inverted U-shape, which showed significant self-administrations compared with the vehicle group at doses of 0.05-0.1 mg/kg/infusion etomidate and the highest intake of 21.1 ± 0.64 infusions per 4 h-session.

Conclusions: These results clearly demonstrate that etomidate has rewarding and reinforcing effects in male rodents, as well as effects on anesthesia and motor inhibition. These findings indicate the possibility of abuse potential in humans using etomidate.