(A) Endogenous NAcsh miR-495 levels are suppressed following 1 and 22 days of cocaine self-administration, as measured by qRT-PCR (Saline: n = 7; SA1: n = 6; SA22: n = 7). *p < 0.05 vs. Saline-yoked. (B) Histological verification of NAcsh cannula placement. (C) NAcsh miR-495 levels are increased in the LV-miR-495 group compared to the LV-GFP group following behavioral testing (n = 4/group). NAcsh miR-495 overexpression reduced responding (D) and intake (E) on a PR schedule of cocaine reinforcement. (F) Cumulative response records of representative rats tested at 1.5 mg/kg/infusion that were closest to their respective group means. Dotted line represents the total number of lever presses emitted once break point was achieved. (G) NAcsh miR-495 overexpression reduced cocaine-seeking behavior during the first three 1-h extinction sessions. (H) NAcsh miR-495 overexpression reduced cocaine-primed reinstatement during the 1-h test session (10 mg/kg, i.p.). LV-GFP: n = 12, LV-miR-495: n = 10. (I–K) Downregulation of Camk2a (LV-GFP: n = 7, LV miR-495: n = 8, p < 0.01) and Bdnf-L and -Pan (n = 6/group, p < 0.01) in NAcsh of miR-495 OE animals after behavioral testing. (L) NAcsh miR-495 overexpression had no effect on responding under a PR schedule of food reinforcement, regardless of whether the rats were food restricted (18g/day) or not (n = 8/group). Error bars indicate SEM. Panels C-H: *p < 0.05 vs. LV-GFP. +p < 0.05 vs. extinction baseline.