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      Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism

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      Neuropsychopharmacology

      Springer Science and Business Media LLC

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          Abstract

          Autism is a severe behavioral disorder characterized by pervasive impairments in social interactions, deficits in verbal and nonverbal communication, and stereotyped, repetitive patterns of behaviors and interests. Recently, a new rodent model of autism was created by exposure of rat fetuses to valproic acid (VPA) on the 12.5th day of gestation (VPA rats). The model has striking anatomical, pathological, and etiological similarities to human data; however, it has not been characterized behaviorally. In order to determine if VPA rats present behavioral aberrations observed in autism, their behavior was extensively evaluated in a battery of tests. The results of the present experiments demonstrate that VPA rats exhibit: (1) lower sensitivity to pain and higher sensitivity to nonpainful stimuli, (2) diminished acoustic prepulse inhibition, (3) locomotor and repetitive/stereotypic-like hyperactivity combined with lower exploratory activity, and (4) decreased number of social behaviors and increased latency to social behaviors. In addition, VPA rats showed delayed maturation, lower body weight, delayed motor development, and attenuated integration of a coordinated series of reflexes, delayed nest-seeking response mediated by olfactory system, and normal negative geotaxis. Interestingly, all behavioral aberrations described in this paper appear before puberty, which could distinguish the VPA rat model of autism from other animal models of neurodevelopmental disorders, especially rodent models of schizophrenia. Our results bring further support to validity of the proposed VPA animal model of autism, suggesting similarities between the observed pattern of behavioral alterations in VPA rats and features of disturbed behavior in autistic patients.

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          Most cited references 49

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          Autism as a strongly genetic disorder: evidence from a British twin study

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            Histoanatomic observations of the brain in early infantile autism.

            Early infantile autism is a behaviorally defined syndrome that is often associated with abnormalities on neurologic examination and seizures. We report on the brain of a 29-year-old autistic man as compared with that of an age- and sex-matched normal control, using gapless sections of whole brain. Abnormalities were found in the hippocampus, subiculum, entorhinal cortex, septal nuclei, mamillary body, selected nuclei of the amygdala, neocerebellar cortex, roof nuclei of the cerebellum, and inferior olivary nucleus.
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              Genetics of autism: complex aetiology for a heterogeneous disorder.

              Since autism was first recognized as a disorder in 1943, speculation about its aetiology has ranged from biological to psychological and back again. After twin studies during the 1970s and 1980s yielded unequivocal evidence for a genetic component, aetiological research in autism began to focus primarily on uncovering the genetic mechanisms involved. The identification of chromosomal abnormalities and Mendelian syndromes among individuals with autism, in conjunction with data from genome screens and candidate-gene studies, has helped to refine the view of the complex genetics that underlies autism spectrum conditions.
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                Author and article information

                Journal
                Neuropsychopharmacology
                Neuropsychopharmacol
                Springer Science and Business Media LLC
                0893-133X
                1740-634X
                January 2005
                July 7 2004
                January 2005
                : 30
                : 1
                : 80-89
                Article
                10.1038/sj.npp.1300518
                15238991
                © 2005

                http://www.springer.com/tdm

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