Stress can trigger, intensify, and prolong drug consumption, as well as reinstate previously extinguished drug-taking behavior by directly impacting a neural circuit often referred to as a reward pathways. Animal models of drug abuse have been used to understand these neural circuits mediating stress-induced drug intake and relapse through examination of cellular and subcellular molecular mechanisms. Several types of intermittent stressors have been shown to induce cross-sensitization to psychomotor stimulants, enhance conditioned place preference under most conditions, increase self-administration of cocaine and amphetamine and induce reinstatement of heroin and cocaine seeking via activation of the mesocorticolimbic dopamine system.