The nucleus accumbens and inhibition in the ventral tegmental area play a causal role in the Kamin blocking effect

The discovery of Kamin blocking led to the idea that associative learning occurs only when there is a mismatch between actual and predicted outcomes, or prediction error. The neural substrates involved in regulating this prediction error during behavioral learning are still not fully elucidated. We investigated in rats the role of the ventral tegmental area and the nucleus accumbens in Kamin blocking. Our blocking paradigm involved three phases: appetitive classical conditioning of a lever cue, conditioning of a compound of the lever cue plus an auditory cue, and testing response to the auditory cue in extinction. We found that disruption of inhibition in the ventral tegmental area by bicuculline, or designer receptor mediated inactivation of the nucleus accumbens, during compound cue conditioning, attenuated Kamin blocking. These results suggest that inhibition in the ventral tegmental area and inhibitory output from the nucleus accumbens are necessary for blocking and make behaviorally significant contributions to the computation of reward prediction error. In addition, we found that inactivating the neurons in the nucleus accumbens during classical conditioning of the lever cue also attenuated blocking, without affecting classical conditioning of the lever. This indicates that learning in the nucleus accumbens is necessary for blocking and reward estimation. Our results reveal a causal role for nucleus accumbens modulated inhibitory inputs to the ventral tegmental area in the blocking effect and suggest that they contribute to computation of reward prediction error during associative learning.