Differential involvement of dopamine in the shell and core of the nucleus accumbens in the expression of latent inhibition to an aversively conditioned stimulus

Abstract

Latent inhibition, the process whereby pre-exposure to a conditioned stimulus without consequence impairs subsequent learning of an association between the conditioned stimulus and an unconditioned stimulus, is reportedly disrupted in both amphetamine-treated rats and in acute schizophrenics. This has led to the suggestion that disruptions in latent inhibition model some of the cognitive impairments associated with hyperactive dopamine transmission as it is expressed in schizophrenic patients. Specifically, fluctuations in dopamine neurotransmission within the nucleus accumbens have been implicated in the mediation of latent inhibition; however, it has not been established whether these dopamine-mediated effects occur in the shell or core subregion of the nucleus. In the present study, 48h after conditioned stimulus-pre-exposed and non-pre-exposed animals experienced 10 pairings of tone and footshock, we measured extracellular levels of dopamine in the shell and core during the expression of latent inhibition to an aversively conditioned tone using in vivo microdialysis. Our results show that pre-exposure to the tone eliminated the conditioned release of dopamine in the shell of the nucleus accumbens and resulted in an attenuated conditioned freezing response to the tone conditioned stimulus. In contrast, dopamine release in the core was not affected by pre-exposure to the tone. These data suggest that it is specifically the shell of the nucleus accumbens in which alterations of dopaminergic tone, whether pharmacologically induced in rodents or the result of disease in humans, may act to disrupt latent inhibition.