(A) Acquisition of heroin SA (FR-1, 30 μg/kg/injection). (B) Mean heroin intake. (C) Between-session dose-response (7.5, 15, 30, 60, 100 μg/kg/infusion; randomized order). (D) Mean heroin intake. (E) Heroin-seeking behavior (cue- and stress-induced) in Penk-infused, GFP-infused, or THC-exposed rats. (F) Penk mRNA levels in NAcsh, NAc core, and caudate-putamen (CPu) following heroin SA. (G) Representative in situ hybridization autoradiograms demonstrating striatal Penk mRNA expression following heroin SA. For all figures, n=5–9/group. Data shown as mean±SEM. *P<0.05; **P<0.01 compared to GFP-expressing controls for each session. AL, active lever; IL, inactive lever, dpm, disintegrations per minute. See also Fig. S1A in the Supplement.