OPEN Foundation

Kappa Opioid Receptor Agonist Mesyl Sal B Attenuates Behavioral Sensitization to Cocaine with Fewer Aversive Side-Effects than Salvinorin A in Rodents.

Share This Post

Share on facebook
Share on linkedin
Share on twitter
Share on email

Abstract

The acute activation of kappa opioid receptors (KOPr) produces antinociceptive and anti-cocaine effects, however, their side-effects have limited further clinical development. Mesyl Sal B is a potent and selective KOPr analogue of Salvinorin A (Sal A), a psychoactive natural product isolated from the plant Salvia divinorum. We assessed the antinociceptive, anti-cocaine, and side-effects of Mesyl Sal B. The anti-cocaine effects are evaluated in cocaine-induced hyperactivity and behavioral sensitization to cocaine in male Sprague Dawley rats. Mesyl Sal B was assessed for anhedonia (conditioned taste aversion), aversion (conditioned place aversion), pro-depressive effects (forced swim test), anxiety (elevated plus maze) and learning and memory deficits (novel object recognition). In male B6.SJL mice, the antinociceptive effects were evaluated in warm-water (50 °C) tail withdrawal and intraplantar formaldehyde (2%) assays and the sedative effects measured with the rotarod performance task. Mesyl Sal B (0.3 mg/kg) attenuated cocaine-induced hyperactivity and behavioral sensitization to cocaine without modulating sucrose self-administration and without producing aversion, sedation, anxiety, or learning and memory impairment in rats. However, increased immobility was observed in the forced swim test indicating pro-depressive effects. Mesyl Sal B was not as potent as Sal A at reducing pain in the antinociceptive assays. In conclusion, Mesyl Sal B possesses anti-cocaine effects, is longer acting in vivo and has fewer side-effects when compared to Sal A, however, the antinociceptive effects are limited.
Kivell, B., Paton, K., Kumar, N., Morani, A., Culverhouse, A., Shepherd, A., … & Prisinzano, T. (2018). Kappa Opioid Receptor Agonist Mesyl Sal B Attenuates Behavioral Sensitization to Cocaine with Fewer Aversive Side-Effects than Salvinorin A in Rodents. Molecules23(10), 2602., 10.3390/molecules23102602
Link to full text

OPEN Foundation

Join ICPR 2022 Online!

ICPR features world-leading experts from many academic disciplines, including psychiatry, psychology, neuroscience, anthropology, ethnobotany, and philosophy who come together to give a scientific conference for academics, therapists, researchers, clinicians, policymakers, and members of the public. Get your ICPR 2022 livestream ticket today and use the code OPENLIVE30 at checkout for a €30 discount.

Learn More

INTERESTED IN PSYCHEDELIC RESEARCH AND THERAPIES?

Subscribe to our new OPEN-Minded newsletter to stay in the loop, hear about our events, and become a part of a community dedicated to advancing psychedelics.

By clicking subscribe, I confirm to receive emails from the OPEN Foundation and agree with its privacy policy.

2 April - New Insights on Addiction & Psychedelic Healing Followed by a Live Q&A!

X