Neonatal functional blockade of the entorhinal cortex results in disruption of accumbal dopaminergic responses observed in latent inhibition paradigm in adult rats.
Latent inhibition (LI) has been found to be disrupted in non-treated patients with schizophrenia. Dopaminergic (DAergic) dysfunctioning is generally acknowledged to occur in schizophrenia. Various abnormalities in the entorhinal cortex (ENT) have been described in patients with schizophrenia. Numerous data also suggest that schizophrenia has a neurodevelopmental origin. The present study was designed to test the hypothesis that reversible inactivation of the ENT during neonatal development results in disrupted DA responses characteristic of LI in adult rats. Tetrodotoxin (TTX) was microinjected locally in the left ENT at postnatal day 8 (PND8). DA variations were recorded in the dorsomedial shell and core parts of the nucleus accumbens (Nacc) using in vivo voltammetry in freely-moving grown-up rats in a LI paradigm. In the first session the animals were pre-exposed (PE) to the conditional stimulus (banana odour) alone. In the second they were aversively conditioned to banana odour. In the third (test) session the following results were obtained in PE animals subjected to temporary inactivation of the ENT at PND8: (1) aversive behaviour was observed in TTX-PE conditioned animals; (2) DA variations in the dorsomedial shell and core parts of the Nacc were similar in TTX-PE and non-pre-exposed conditioned rats. These findings strongly suggest that neonatal disconnection of the ENT disrupts LI in adult animals. They may further our understanding of the pathophysiology of schizophrenia.
Peterschmitt
Y
Y
INSERM U 666 and Institute of Physiology, Louis Pasteur University, Faculty of Medicine, 11 rue Humann, 67085 Strasbourg CEDEX, France.
Meyer
F
F
Louilot
A
A
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology; D003214:Conditioning, Classical; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods; D018728:Entorhinal Cortex / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000378:metabolism*; D011042:Poisons / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia; D013779:Tetrodotoxin / Q000378:metabolism
D011042:Poisons; D013779:Tetrodotoxin; D004298:Dopamine