Original Article
Neuropsychopharmacology (2006) 31, 36–46. doi:10.1038/sj.npp.1300767; published online 25 May 2005
Preclinical Research
Environmental Enrichment Reverses Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Issues for a Therapeutic Approach in Autism
Tomasz Schneider1, Joanna Turczak1 and Ryszard Przew
ocki1
Correspondence: Professor R Przewlocki, Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Sm
tna Str, 31-343 Kraków, Poland. Tel: +4812 6623218; Fax: +4812 6374500; E-mail: nfprzewl@cyf-kr.edu.pl
Received 25 October 2004; Revised 9 March 2005; Accepted 10 March 2005; Published online 25 May 2005.
Abstract
Environmental enrichment has been repeatedly shown to affect multiple aspects of brain function, and is known to improve cognitive, behavioral, and histopathological outcome after brain injuries. The purpose of the present experiments was to determine the effect of an enriched environment on behavioral aberrations observed in male rats exposed to valproic acid on day 12.5 of gestation (VPA rats), and proposed on the basis of etiological, anatomical, and behavioral data as an animal model of autism. Environmental enrichment reversed almost all behavioral alterations observed in the model. VPA rats after environmental enrichment (VPA-E) compared to VPA rats reared in standard conditions have higher sensitivity to pain and lower sensitivity to nonpainful stimuli; stronger acoustic prepulse inhibition; lower locomotor, repetitive/stereotypic-like activity, and enhanced exploratory activity; decreased anxiety; increased number of social behaviors; and shorter latency to social explorations. In comparison with control animals (Con), VPA-E rats exhibited increased number of pinnings in adolescence and social explorations in adulthood, and were less anxious in the elevated plus maze. Similar differences in social behavior and anxiety were observed between control rats exposed to environmental enrichment (Con-E) and control group reared in standard conditions. These results suggest that postnatal environmental manipulations can counteract the behavioral alterations in VPA rats. We propose environmental enrichment as an important tool for the treatment of autism spectrum disorders.
Keywords:
autism, rats, valproic acid, environmental enrichment
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