Fig. 2: Experiment 2: Systemic ERβ agonism enhances heroin-cue EMR in both sexes.

A Experiment 2 timeline. B Daily ANPs during heroin self-administration in males and females. ANPs did not differ between the sexes. C Heroin intake (mg heroin/kg body weight) during self-administration. Females took more heroin than males (ME of sex). D Total ANPs during the 1 h cued extinction session. Females had greater ANPs than males. Systemically administered DPN had no effect on ANPs during extinction in either sex. E Quarterly ANPs during the cued extinction session. Veh and DPN-treated groups were collapsed since DPN had no effect. Female ANPs were increased relative to males, particularly early on (time x sex interaction). F Total ANPs during the 1 h EMR test. ANPs were impacted by DPN (ME of DPN) and sex (ME of sex). DPN, administered systemically the day prior, decreased ANPs in both sexes relative to Veh controls. Veh females had greater ANPs than all other groups. G Difference scores comparing ANPs during extinction to ANPs during test. Difference scores were also impacted by DPN (ME of DPN) and sex (ME of sex). DPN decreased difference scores in both sexes relative to sex matched Veh controls. All data are shown as mean ± SEM; n = 7–8 rats/group; *p < 0.05, ***p < 0.001, ****p < 0.0001, $p < 0.05 versus Veh, #p < 0.05 versus all other groups. ANPs, active nose pokes; DPN, diarylpropionitrile (ERβ agonist); EMR, extinction memory recall; FR, fixed ratio; INPs, inactive nose pokes; ME, main effect; Veh, vehicle.