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Schizophrenia would result from a defective connectivity between several integrative regions as a consequence of neurodevelopmental failure. Various anomalies reminiscent of early brain development disturbances have been observed in patients' left ventral subiculum of the hippocampus (SUB). Numerous data support the hypothesis of a functional dopaminergic dysregulation in schizophrenia. The common target structure for the action of antipsychotics appears to be a subregion of the ventral striatum, the dorsomedial shell part of the nucleus accumbens. Latent inhibition, a cognitive marker of interest for schizophrenia, has been found to be disrupted in acute patients. The present study set out to investigate the consequences of a neonatal functional inactivation of the left SUB by tetrodotoxin (TTX) in 8-day-old rats for the latent inhibition-related dopaminergic responses, as monitored by in vivo voltammetry in freely moving adult animals (11 weeks) in the left core and dorsomedial shell parts of the nucleus accumbens in an olfactory aversion procedure. Results obtained during the retention session of a three-stage latent inhibition protocol showed that the postnatal unilateral functional blockade of the SUB was followed in pre-exposed TTX-conditioned adult rats by a disruption of the behavioral expression of latent inhibition and induced a total and a partial reversal of the latent inhibition-related dopaminergic responses in the dorsomedial shell and core parts of the nucleus accumbens, respectively. The present data suggest that neonatal inactivation of the SUB has more marked consequences for the dopaminergic responses recorded in the dorsomedial shell part, than in the core part of the nucleus accumbens. These findings may provide new insight into the pathophysiology of schizophrenia.

neuropsychopharmacology

Latent Inhibition-Related Dopaminergic Responses in the Nucleus Accumbens are Disrupted Following Neonatal Transient Inactivation of the Ventral Subiculum