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Fifteen to 30 min after the start of behavioral measurements, a 3. 0 mg/kg dose of RU 24213 produced a marked increase in linear locomotion, circling, rearing and grooming behaviors. Although the mu-selective opioid peptide [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) (0. 003 and 0. 01 microgram) itself did not significantly affect behaviors, DAGO (0. 01 microgram) antagonized the RU 24213 (3. 0 mg/kg)-induced increase in behaviors such as linear locomotion, circling, rearing, and grooming.
The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, ß-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism.