title: Swim stress exaggerates the hyperactive mesocortical dopamine system in a rodent model of autism.
abstract: Several clinical reports have suggested that there is a hyperactivation of the dopaminergic system in people with autism. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we measured dopamine (DA) levels in samples collected from the frontal cortex (FC) using in vivo microdialysis and HPLC. The basal DA level in FC was significantly higher in VPA-exposed rats relative to controls. Since the mesocortical DA system is known to be sensitive to physical and psychological stressors, we measured DA levels in FC before, during, and after a 60-min forced swim test (FST). There were further gradual increases in FC DA levels during the FST in the VPA-exposed rats, but not in the control rats. Behavioral analysis during the last 10 min of the FST revealed a significant decrease in active, escape-oriented behavior and an increase in immobility, which is thought to reflect the development of depressive behavior that disengages the animal from active forms of coping with stressful stimuli. These results suggest that this rodent model of autism exhibits a hyperactive mesocortical DA system, which is exaggerated by swim stress. This abnormality may be responsible for depressive and withdrawal behavior observed in autism.
authors.affiliation: Department of Physiology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Nakasato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Seki
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tsujino
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umino
authors.forename: Hideho
authors.initials: H
authors.lastname: Arita
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use; D001321:Autistic Disorder / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D017551:Microdialysis; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology*; D013550:Swimming; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D012701:Serotonin; D014635:Valproic Acid; D004298:Dopamine