Cocaine self-administration. Decreasing activity in mPFC afferents to NAc modulates drug seeking. There were no differences between groups in active (circles) and inactive (squares) lever responses (a, left panel) and number of earned infusions (b, left panel) during baseline progressive ratio (PR) cocaine self-administration (last 3 sessions before testing). CNO-mediated activation of hM4Di in corticostriatal afferents had no effect on lever responses (a, right panel) or number of earned infusions (b, right panel). Rats that had hM4Di activation during PR showed a significant increase in the number of active lever responses during the first 2 sessions of extinction training (c, *P<0.05 versus GFP group) as well as following a cocaine prime (d, *P<0.05 versus GFP group). CNO pretreatment before a cocaine prime significantly attenuated active lever responding only in the hM4Di group (d, #P<0.05 versus V-treated hM4Di group). Data represent mean±SEM. Black symbols in line graphs represent the hM4Di group and white symbols represent the GFP controls. XNote that pretreatments (V or C) were counterbalanced across rats during reinstatement tests. SAL: saline injection; COC: cocaine injection; V: vehicle pretreatment; C: CNO pretreatment. N=5–7 group.