Behavior and serotonergic disorders in rats exposed prenatally to valproate: a model for autism.
In order to explore whether some aspects of the autistic phenotype could be related to impairment of the serotonergic system, we chose an animal model which mimics a potential cause of autism, i.e. rats exposed to valproate (VPA) on the 9th embryonic day (E9). Previous studies have suggested that VPA exposure in rats at E9 caused a dramatic shift in the distribution of serotonergic neurons on postnatal day 50 (PND50). Behavioral studies have also been performed but on rats that were exposed to VPA later (E12.5). Our aim was to test whether VPA exposure at E9 induces comparable behavioral impairments than at E12.5 and causes serotonergic impairments which could be related to behavioral modifications. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions and hyperlocomotor activity in juvenile male rats. The serotonin levels of these animals at PND50 were decreased (-46%) in the hippocampus, a structure involved in social behavior. This study suggests that VPA could have a direct or indirect action on the serotonergic system as early as the progenitor cell stage. Early embryonic exposure to VPA in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological hypotheses.
Dufour-Rainfray
Diane
D
CHRU de Tours, Tours, France. ddufourrainfray@yahoo.fr
Vourc'h
Patrick
P
Le Guisquet
Anne-Marie
AM
Garreau
Lucette
L
Ternant
David
D
Bodard
Sylvie
S
Jaumain
Emilie
E
Gulhan
Zuhal
Z
Belzung
Catherine
C
Andres
Christian R
CR
Chalon
Sylvie
S
Guilloteau
Denis
D
D000818:Animals; D001321:Autistic Disorder / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018682:GABA Agents / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012919:Social Behavior; D013997:Time Factors; D014635:Valproic Acid / Q000633:toxicity*
D018682:GABA Agents; D016601:RNA-Binding Proteins; C482440:Sert1 protein, rat; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014635:Valproic Acid