Fig. 4. Remifentanil-induced deficits in cognitive flexibility.

a Timeline of behavioral assessments following 10–16 or 25–30-day self-administration and schematic of operant set-shifting procedure depicting levers (gray), dipper (white), cue location (yellow), and correct response (star). b, e Testing following 10–16 days of self-administration in males and females. b Number of days to pass lever training criterion (2 consecutive days ≤ 5 omissions) was similar acrosss treatment and sex. c Number of trials to criterion during a visual cue test also showed no significant effect of sex, treatment, or interaction. d Number of trials to criterion during the extradimensional (ED) shift test showed remifentanil females required more trials vs. saline females and remifentanil males, whereas performance in remifentanil vs. saline males was similar. e Number of trials to criterion during a reversal test showed no significant effect of sex, treatment, or interaction. f–h Testing following 25–30 days of self-administration in males. f, g No difference was observed in number of days to pass lever training criterion or trials to reach criterion during a visual cue test. h During the ED test, remifentanil males required more trials to reach criterion compared to saline. *p < 0.05, **p < 0.01.