title: Effect of prefrontal cortex inactivation on behavioral and neurochemical abnormalities in rats with excitotoxic lesions of the entorhinal cortex.
abstract: Morphological studies report reductions in the volume of medial temporal lobe structures and the prefrontal cortex in subjects with schizophrenia. The present study was performed to clarify the role of prefrontal-temporo-limbic system in the manifestation of psychosis, using entorhinal cortical lesion rats as a vulnerability animal model. Quinolinic acid (lesion group) or phosphate buffer (sham group) was infused into the left entorhinal cortex (EC) of male Wistar rats. On the 28th postoperative day, methamphetamine (MAP; 1 mg/kg, i.p.)-induced dopamine (DA) release in the nucleus accumbens (NAC) and the basolateral amygdala (BLA), as well as locomotor activity and prepulse inhibition (PPI), was measured following microinfusion of lidocaine or the cerebrospinal fluid (CSF) into the medial prefrontal cortex (mPFC). Lesions of the EC resulted in enhancement of MAP-induced DA release in the NAC and BLA. Further analysis revealed that the enhancement by EC lesions of MAP-induce DA release in the NAC was particularly evident in the lidocaine-infused rats. EC lesions also enhanced MAP-induced locomotor activity, especially in the lidocaine-treated animals. By contrast, infusion of lidocaine into mPFC attenuated MAP-induced DA release in the BLA, irrespective of the lesion status. Both EC lesions and lidocaine infusion disrupted PPI. These results indicate that inactivation of the mPFC, as well as structural abnormalities in the EC, leads to dysregulation of DAergic neurotransmissions in the limbic regions. The implications of these findings in relation to the neural basis for psychosis vulnerability are discussed.
authors: Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Science, Toyama, Japan. uehara@med.u-toyama.ac.jp
authors: Takashi
authors: T
authors: Uehara
authors: Tomiki
authors: T
authors: Sumiyoshi
authors: Tadasu
authors: T
authors: Matsuoka
authors: Hiroko
authors: H
authors: Itoh
authors: Masayoshi
authors: M
authors: Kurachi
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D003714:Denervation; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008012:Lidocaine / Q000494:pharmacology; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000779:Anesthetics, Local; D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; D008012:Lidocaine; D017378:Quinolinic Acid; D004298:Dopamine