The mixed-action delta/mu opioid agonist MMP-2200 does not produce conditioned place preference but does maintain drug self-administration in rats, and induces in vitro markers of tolerance and dependence

Pharmacology, Biochemistry, and Behavior
Glenn W StevensonEdward J Bilsky

Abstract

Previous work in our laboratories provides preclinical evidence that mixed-action delta/mu receptor glycopeptides have equivalent efficacy for treating pain with reduced side effect profiles compared to widely used mu agonist analgesics such as morphine. This study evaluated the rewarding and reinforcing effects of a lead candidate, mixed-action delta/mu agonist MMP-2200, using a conditioned place preference assay as well as a drug self-administration procedure in rats. In place conditioning studies, rats underwent a 2-week conditioning protocol and were then tested for chamber preference. Rats receiving MMP-2200, at previously determined analgesic doses, could not distinguish between the drug and saline-paired chamber, whereas rats receiving the opioid agonist morphine showed a strong preference for the morphine-paired chamber. In self-administration studies, rats were trained to respond for the high efficacy mu opioid receptor agonist fentanyl on an FR5 schedule of reinforcement. Following complete dose-response determinations for fentanyl, a range of doses of MMP-2200 as well as morphine were tested. Relative to the mu agonist morphine, MMP-2200 maintained a significantly lower number of drug infusions. To begin investigatin...Continue Reading

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Citations

Dec 26, 2016·Peptides·Richard J Bodnar
Jun 23, 2018·Pharmacology Research & Perspectives·Jai Shankar K YadlapalliWilliam E Fantegrossi
Jun 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Meining WangKenner C Rice
Sep 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ariana C Brice-TuttJane V Aldrich
Apr 19, 2019·ACS Medicinal Chemistry Letters·Azzurra StefanucciAdriano Mollica
Nov 21, 2020·Journal of Medicinal Chemistry·Christine RobinsonMarco Pravetoni

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