title: Enhanced locomotor activity in rats with excitotoxic lesions of the entorhinal cortex, a neurodevelopmental animal model of schizophrenia: behavioral and in vivo microdialysis studies.
abstract: In order to examine the construct validity of rats with excitotoxic damage of the left entorhinal cortex (EC) as an animal model of schizophrenia, we measured dopamine (DA)-related behaviors and methamphetamine (MAP)-induced DA release in the accumbens nucleus (NAC) in these animals. Quinolinic acid (lesion group) or phosphate buffer (sham group) was infused into the left EC of adolescent (postnatal 7 weeks) male Wistar rats. On the 14th and 28th postoperative day, spontaneous and MAP (1 mg/kg, i.p.)-induced locomotor activities, as well as MAP-induced stereotypy, were measured. The lesioned rats exhibited significantly greater spontaneous or MAP-induced locomotor activity on both of the postoperative days than did sham-operated animals, while EC lesions did not affect MAP-induced stereotypy on either occasion. MAP (1 mg/kg, i.p.)-induced DA release in NAC was measured by in vivo microdialysis on the 28th postoperative day. Lesioned rats did not show a significant change in MAP (1 mg/kg, i.p.)-induced DA release in NAC compared to sham-operated animals. These results suggest that excitotoxic damage of the left EC produces behavioral changes consistent with altered mesolimbic dopaminergic transmissions, possibly mediated by postsynaptic supersensitivity.
authors.affiliation: Department of Neuropsychiatry, Toyama Medical and Pharmaceutical University, School of Medicine, 2630 Sugitani, Toyama 930-0194, Japan. sumiyo@ms.toyama-mpu.ac.jp
authors.forename: Tomiki
authors.initials: T
authors.lastname: Sumiyoshi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsunoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Uehara
authors.forename: Kodai
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Itoh
authors.forename: Chika
authors.initials: C
authors.lastname: Sumiyoshi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kurachi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D015259:Dopamine Agents / Q000633:toxicity; D018728:Entorhinal Cortex / Q000502:physiology*; D008297:Male; D008694:Methamphetamine / Q000633:toxicity; D017551:Microdialysis; D009043:Motor Activity / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012565:Schizophrenic Psychology; D013239:Stereotyped Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D015259:Dopamine Agents; D008694:Methamphetamine; D017378:Quinolinic Acid; D004298:Dopamine