title: Abnormal stress responsivity in a rodent developmental disruption model of schizophrenia.
abstract: Although numerous studies have implicated stress in the pathophysiology of schizophrenia, less is known about how the effects of stress interact with genetic, developmental, and/or environmental determinants to promote disease progression. In particular, it has been proposed that in humans, stress exposure in adolescence could combine with a predisposition towards increased stress sensitivity, leading to prodromal symptoms and eventually psychosis. However, the neurobiological substrates for this interaction are not fully characterized. Previous work in our lab has demonstrated that rats born to dams administered with the DNA-methylating agent methylazoxymethanol acetate (MAM) at gestational day 17 exhibit as adults behavioral and anatomical abnormalities consistent with those observed in patients with schizophrenia. Here, we examined behavioral and neuroendocrine responses to stress in the MAM model of schizophrenia. MAM-treated male rats were exposed to acute and repeated footshock stress at prepubertal, peripubteral, and adult ages. Ultrasonic vocalizations (USVs), freezing, and corticosterone responses were quantified. We found that juvenile MAM-treated rats emitted significantly more calls, spent more time vocalizing, emitted calls at a higher rate, and showed more freezing in response to acute footshock stress when compared with their saline (SAL) treated counterparts, and that this difference is not present in older animals. In addition, adolescent MAM-treated animals displayed a blunted HPA axis corticosterone response to acute footshock that did not adapt after 10 days of stress exposure. These data demonstrate abnormal stress responsivity in the MAM model of schizophrenia and suggest that these animals are more sensitive to the effects of stress in youth.
authors: Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Eric C
authors: EC
authors: Zimmerman
authors: Mark
authors: M
authors: Bellaire
authors: Samuel G
authors: SG
authors: Ewing
authors: Anthony A
authors: AA
authors: Grace
mesh_terms: D000367:Age Factors; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005260:Female; D046353:Immobility Response, Tonic / Q000502:physiology; D008297:Male; D008746:Methylazoxymethanol Acetate; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D051381:Rats; D012559:Schizophrenia / Q000097:blood / Q000139:chemically induced* / Q000150:complications; D013315:Stress, Psychological / Q000097:blood / Q000150:complications / Q000503:physiopathology* / Q000523:psychology*; D014828:Vocalization, Animal / Q000502:physiology
chemical_list: D008746:Methylazoxymethanol Acetate; D003345:Corticosterone
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