(A) Overview of experiment. Animals underwent heroin SA for 8 days. On days 9–11, animals were pretreated with 5-HT2AR antagonist ketanserin IP 15 min prior to SA. After 17D abstinence, animals underwent 3 relapse tests on consecutive days and were pretreated with ketanserin 15 min prior to the test. (B-H) Shown are drug-paired active or inactive lever presses (B-D, G) and heroin infusions during SA (E, F, H). (B-F) SA behavior for each treatment group, prior to ketanserin treatment for days 1–8. Animals were split into treatment groups on day 8, with no significant differences observed in lever responses (D) or heroin infusions (F). (G-H) Heroin SA lever responses (G) and infusions (H) on days 9–11, following pretreatment with ketanserin. (I-K) Active and inactive lever presses during relapse tests on subsequent days (R1, R2, R3) for animals that were pretreated with ketanserin prior to the relapse test. (J, K) Shown are active lever presses from panel I combined. Error bars indicate mean +/− S.E.M. Post hoc test indicated directly above individual histograms, * p<0.05; n=5–12/group.