Temporal-difference prediction errors and Pavlovian fear conditioning: role of NMDA and opioid receptors

Three experiments studied temporal-difference (TD) prediction errors during Pavlovian fear conditioning. In Stage I, rats received conditioned stimulus A (CSA) paired with shock. In Stage II, they received pairings of CSA and CSB with shock that blocked learning to CSB. In Stage III, a serial overlapping compound, CSB --> CSA, was followed by shock. The change in intratrial durations supported fear learning to CSB but reduced fear of CSA, revealing the operation of TD prediction errors. N-methyl- D-aspartate (NMDA) receptor antagonism prior to Stage III prevented learning, whereas opioid receptor antagonism selectively affected predictive learning. These findings support a role for TD prediction errors in fear conditioning. They suggest that NMDA receptors contribute to fear learning by acting on the product of predictive error, whereas opioid receptors contribute to predictive error.