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For almost two decades schizophrenia has been considered to be a functionaldisconnection disorder. This functional disconnectivity between several brainregions could have a neurodevelopmental origin. Various approaches suggest theventral subiculum (SUB) is a particular target region for neurodevelopementaldisturbances in schizophrenia. It is also commonly acknowledged that there is astriatal dopaminergic (DA) dysregulation in schizophrenia which may depend on asubiculo-striatal disconnection involving glutamatergic NMDA receptors. Thepresent study was designed to investigate, in adult rats, the effects of thenon-competitive NMDA receptor antagonist ketamine on DA responses in theventral striatum, or, more specifically, the core part of the nucleus accumbens(Nacc), following postnatal functional inactivation of the SUB. Functionalinactivation of the left SUB was carried out by local tetrodotoxin (TTX)microinjection at postnatal day 8 (PND8), i.e. at a critical point in theneurodevelopmental period. DA variations were recorded using in vivovoltammetry in freely moving adult rats (11 weeks). Locomotor activity wasrecorded simultaneously with the extracellular levels of DA in the core part ofthe Nacc. Data obtained during the present study showed that afteradministration of ketamine, the two indexes were higher in TTX animals than PBSanimals, the suggestion being that animals microinjected with TTX in the leftSUB at PND8 present greater reactivity to ketamine than animals microinjectedwith PBS. These findings could provide new information regarding theinvolvement of NMDA glutamatergic receptors in the core part of the Nacc in thepathophysiology of schizophrenia.

biorxiv (cold spring harbor laboratory)

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