Blockade of dopamine activity in the nucleus accumbens impairs learning extinction of conditioned fear

Abstract

Three experiments used rats to investigate the role of dopamine activity in learning to inhibit conditioned fear responses (freezing) in extinction. In Experiment 1, rats systemically injected with the D2 dopamine antagonist, haloperidol, froze more across multiple extinction sessions and on a drug-free retention test than control rats. In Experiment 2, rats extinguished under an intracerebroventricular (ICV) infusion of haloperidol suppressed fear responses across extinction but froze more on a subsequent drug-free retention test than control rats. In Experiment 3, rats extinguished under an infusion of haloperidol in the nucleus accumbens were impaired in suppressing fear responses across extinction and froze more on subsequent drug-free retention test than control rats. These results show that learning to inhibit fear responses in extinction requires dopamine activity in the nucleus accumbens. They were interpreted to mean that dopaminergic activity in the nucleus accumbens regulates the prediction error required for learning to inhibit fear responses in extinction. © 2010 Cold Spring Harbor Laboratory Press.