An important aspect of goal-directed action selection is differentiating between actions that are more or less likely to be reinforced. With repeated performance or psychostimulant exposure, however, actions can assume stimulus-elicited-or "habitual"-qualities that are resistant to change. We show that selective knockdown of prelimbic prefrontal cortical Brain-derived neurotrophic factor (Bdnf) increases sensitivity to response-outcome associations, blocking habit-like behavioral inflexibility. A history of adolescent cocaine exposure, however, occludes the "beneficial" effects of Bdnf knockdown. This finding highlights a challenge in treating addiction-that drugs of abuse may bias decision-making toward habit systems even in individuals with putative neurobiological resiliencies.