A G protein–biased KOR agonist does not display anhedonia-like effects. (A) The response for different frequencies of brain stimulation reward by C57BL/6J mice treated with 1 mg/kg drug. All treatments showed a rightward shift in the average rate-frequency curves compared with vehicle; U69593 had the largest effect, followed by sal A, and then RB-64 (n = 13 for all conditions). (B) Dose-response relationship for the effects of U69593, sal A, and RB-64 on the BSR. Results are presented as mean percentages of preinjection baseline during the four 15-minute postinjection response series ± S.E.M. *Significance (P < 0.05) of drug versus vehicle. #Significance (P < 0.05) of drug compared with another drug treatment. (C) Dose-response relationship for the effects of U69593, sal A, and RB-64 on the maximum response rate (MAX) in C57BL/6J mice. Results are presented as mean percentage of preinjection baseline during the four 15-minute postinjection response periods ± S.E.M. *Significance (P < 0.05) versus vehicle. #Significance (P < 0.05) versus a separate drug treatment. n = 13 for all treatment conditions.