title: Neonatal medial prefrontal cortex lesion enhances the sensitivity of the mesoaccumbal dopamine system.
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 affect 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 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 the core region, neonatal mPFC lesions altered the discharge pattern within the 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 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.
authors.affiliation: Department of Neuropharmacology, Brain Research Institute, University of Bremen, POB 330440, 28334 Bremen, Germany. mbennay@uni-bremen.de
authors.forename: Mustapha
authors.initials: M
authors.lastname: Bennay
authors.forename: Manuela
authors.initials: M
authors.lastname: Gernert
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schwabe
authors.forename: Thomas
authors.initials: T
authors.lastname: Enkel
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004594:Electrophysiology; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000293:injuries*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004298:Dopamine