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. Striatal dopaminergic dysregulation in schizophrenia may result from a dysconnection between the prefrontal cortex and the striatum (dorsal and ventral) involving glutamatergic N-methyl-d-aspartate (NMDA) receptors. In the context of animal modeling of the pathophysiology of schizophrenia, the present study was designed to investigate the effects of MK 801 (dizocilpine) on locomotor activity and dopaminergic responses in the left core part of the nucleus accumbens (ventral striatum) in adult rats following neonatal tetrodotoxin inactivation of the left prefrontal cortex (infralimbic/prelimbic region) at postnatal day 8. Dopaminergic variations were recorded in the nucleus accumbens by means of in vivo voltammetry in freely moving adult animals. Following MK 801 administration, and in comparison to control (PBS) animals, animals microinjected with tetrodotoxin display locomotor hyperactivity and increased extracellular dopamine levels in the core part of the nucleus accumbens. These findings suggest neonatal functional inactivation of the prefrontal cortex may lead to a dysregulation of dopamine release in the core part of the nucleus accumbens involving NMDA receptors. The results obtained may provide new insight into the involvement of NMDA receptors in the pathophysiology of schizophrenia and suggest that future studies should look carefully at the core of the nucleus accumbens.
['Tagliabue|Emmanuelle|E|', 'Pouvreau|Tiphaine|T|', 'Eybrard|Séverine|S|', 'Meyer|Francisca|F|', 'Louilot|Alain|A|']
D000818:Animals D000831:Animals, Newborn D003342:Corpus Striatum D004195:Disease Models, Animal D016291:Dizocilpine Maleate D004298:Dopamine D015259:Dopamine Agents D008124:Locomotion D008297:Male D017072:Neostriatum D009714:Nucleus Accumbens D017397:Prefrontal Cortex D051381:Rats D017207:Rats, Sprague-Dawley D016194:Receptors, N-Methyl-D-Aspartate D012559:Schizophrenia D013779:Tetrodotoxin
Nucleus accumbens Schizophrenia Animal modeling MK 801 In vivo voltammetry Neonatal prefrontal inactivation