Latent inhibition of conditioned dopamine release in rat nucleus accumbens.

Classical conditioning both to rewarding and to aversive stimuli is sensitive to drugs which act on the dopaminergic system: amphetamine enhances conditioning and neuroleptics attenuate it. Many lines of evidence point to the nucleus accumbens as being part of an anatomical substrate for reward. We have examined the release of dopamine in the nucleus accumbens during classical aversive conditioning using microdialysis in the unrestrained rat. Two mild footshocks caused a release of dopamine, which was potentiated when each footshock was immediately preceded by a novel tone or light stimulus. Presentation of either of these stimuli after conditioning elicited an increase in dopamine, only to that stimulus which had been conditioned; presentation of either stimulus after footshock alone without conditioning produced no dopamine response. Latent inhibition is a process whereby pre-exposure to a stimulus without consequence impairs learning about that stimulus at subsequent conditioning. This process too is believed to be under the control of dopaminergic systems, particularly in nucleus accumbens. Pre-exposure to the tone stimulus both markedly attenuated the potentiation of dopamine release at conditioning and abolished the conditioned release of dopamine at subsequent tone presentation. This is the first report of direct measurement of potentiated dopamine release during conditioning, and may provide a neurochemical basis for the effects of dopaminergic drugs on conditioning and latent inhibition. The results also support the hypothesis that disrupted latent inhibition in schizophrenia reflects increased mesolimbic dopamine function.