MK-801-induced behavioral and dopaminergic responses in the shell part of the nucleus accumbens in adult male rats are disrupted after neonatal blockade of the ventral subiculum.

The present study was conducted in the context of animal modeling of schizophrenia. It investigated in adult male rats, after transient neonatal blockade of the ventral subiculum (VSub), the impact of a very specific non-competitive antagonist of NMDA receptors (MK-801) on locomotor activity and dopaminergic (DAergic) responses in the dorsomedial shell part of the nucleus accumbens (Nacc), a striatal subregion described as the common target region for antipsychotics. The functional neonatal inactivation of the VSub was achieved by local microinjection of tetrodotoxin (TTX) at postnatal day 8 (PND8).

Postnatal functional inactivation of the ventral subiculum enhances dopaminergic responses in the core part of the nucleus accumbens following ketamine injection in adult rats.

For almost two decades schizophrenia has been considered to be a functional disconnection disorder. This functional disconnectivity between several brain regions could have a neurodevelopmental origin. Various approaches suggest the ventral subiculum (SUB) is a particular target region for neurodevelopemental disturbances in schizophrenia.

Dopaminergic responses in the core part of the nucleus accumbens to subcutaneous MK801 administration are increased following postnatal transient blockade of the prefrontal cortex.

Schizophrenia is a complex and devastating neuropsychiatric disease thought to result from impaired connectivity between several integrative regions, stemming from developmental failures. In particular, the left prefrontal cortex of schizophrenia patients seems to be targeted by such early developmental disturbances. Data obtained over the last three decades support the hypothesis of a dopaminergic dysfunction in schizophrenia.

Neonatal Prefrontal Inactivation Results in Reversed Dopaminergic Responses in the Shell Subregion of the Nucleus Accumbens to NMDA Antagonists.

Striatal dopaminergic dysregulation in schizophrenia could result from a prefronto-striatal dysconnectivity, of neurodevelopmental origin, involving N-methyl-d-aspartate (NMDA) receptors. The dorsomedian shell part of the nucleus accumbens is a striatal subregion of particular interest inasmuch as it has been described as the common target region for antipsychotics. Moreover, NMDA receptors located on the dopaminergic endings have been reported in the shell.