Neonatale Läsionen des präfrontalen Cortex der Ratte: Effekte auf die Neurophysiologie des Nucleus accumbens
Date Issued
2004-05-14
Author(s)
Supervisors
Referees
Roth, Gerhard
Abstract
Neurodevelopmental models of schizophrenia posit that early brain damage leads to dys- or misconnection effects possibly altering synaptic transmission in brain sites distal of the lesion. We tested the hypothesis that neonatal medial prefrontal cortex (mPFC) lesions affects the sensitivity of the mesoaccumbal dopamine (DA) system. Using extracellular single unit recordings combined with systemic application of the DA agonist apomorphine, followed by the D2 receptor antagonist haloperidol or the D1 receptor antagonist SCH23390, we compared electrophysiological properties of nucleus accumbens (NAC) core and shell neurons after bilateral excitotoxic lesions of mPFC induced at postnatal day 7 or in adult rats. Whereas animals with adult mPFC lesions showed an altered discharge pattern within core region, neonatal mPFC lesions altered the discharge pattern within shell region. Subcutaneous administration of apomorphine (4 mg/kg) reduced accumbal firing rate in 77% of all neurons. Onset and magnitude of apomorphine-induced inhibition of neuronal activity was faster and stronger in rats with neonatal but not adult mPFC lesions in both core and shell regions. Apomorphine-induced inhibition was partially reversed by of 0.1 mg/kg haloperidol only in core region of neonatal lesioned rats. Apomorphine-induced excitation of neuronal activity (in 21% of all neurons) was reversed by the D1 receptor antagonist SCH23390 (0.1 mg/kg) in all excited neurons. These data support the hypothesis that neonatal but not adult lesions of mPFC alter cortico-striatal networks and suggest that disturbance of mPFC development leads to neurodevelopmental changes in mesoaccumbal DA system during adulthood.
Subjects
mPFC lesions
;
nucleus accumbens core
;
nucleus accumbens shell
;
apomorphine
;
haloperidol
;
single unit recordings
;
firing pattern
;
schizophrenia.
Institution
Type
Dissertation
Secondary publication
No
Language
German
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