PMID- 27708559
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 10
DP  - 2016
TI  - Does Prenatal Valproate Interact with a Genetic Reduction in the Serotonin 
      Transporter? A Rat Study on Anxiety and Cognition.
PG  - 424
LID - 424
AB  - There is ample evidence that prenatal exposure to valproate (or valproic acid, 
      VPA) enhances the risk of developing Autism Spectrum Disorders (ASD). In line 
      with this, a single injection of VPA induces a multitude of ASD-like symptoms in 
      animals, such as rats and mice. However, there is equally strong evidence that 
      genetic factors contribute significantly to the risk of ASD and indeed, like most 
      other psychiatric disorders, ASD is now generally thought to results from an 
      interaction between genetic and environmental factors. Given that VPA 
      significantly impacts on the serotonergic system, and serotonin has strong 
      biochemical and genetic links to ASD, we aimed to investigate the interaction 
      between genetic reduction in the serotonin transporter and prenatal valproate 
      administration. More specifically, we exposed both wildtype (SERT(+/+)) rats and 
      rats heterozygous for the serotonin transporter deletion (SERT(+/-)) to a single 
      injection of 400 mg/kg VPA at gestational day (GD) 12. The offspring, in 
      adulthood, was assessed in four different tests: Elevated Plus Maze and Novelty 
      Suppressed Feeding as measures for anxiety and prepulse inhibition (PPI) and 
      latent inhibition as measures for cognition and information processing. The 
      results show that prenatal VPA significantly increased anxiety in both paradigm, 
      reduced PPI and reduced conditioning in the latent inhibition paradigm. However, 
      we failed to find a significant gene-environment interaction. We propose that 
      this may be related to the timing of the VPA injection and suggest that whereas 
      GD12 might be optimal for affecting normal rat, rats with a genetically 
      compromised serotonergic system may be more sensitive to VPA at earlier time 
      points during gestation. Overall our data are the first to investigate gene (*) 
      environmental interactions in a genetic rat model for ASD and suggest that timing 
      may be of crucial importance to the long-term outcome.
FAU - Ellenbroek, Bart A
AU  - Ellenbroek BA
AD  - School of Psychology, Victoria University of Wellington Wellington, New Zealand.
FAU - August, Caren
AU  - August C
AD  - School of Psychology, Victoria University of Wellington Wellington, New Zealand.
FAU - Youn, Jiun
AU  - Youn J
AD  - School of Psychology, Victoria University of Wellington Wellington, New Zealand.
LA  - eng
PT  - Journal Article
DEP - 20160921
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC5030776
OTO - NOTNLM
OT  - Autism Spectrum Disorder
OT  - SERT Knock-out
OT  - animal model
OT  - gene-environment interaction
OT  - latent inhibition
OT  - novelty suppressed feeding
OT  - prepulse inhibition
EDAT- 2016/10/07 06:00
MHDA- 2016/10/07 06:01
PMCR- 2016/01/01
CRDT- 2016/10/07 06:00
PHST- 2016/06/28 00:00 [received]
PHST- 2016/08/30 00:00 [accepted]
PHST- 2016/10/07 06:00 [entrez]
PHST- 2016/10/07 06:00 [pubmed]
PHST- 2016/10/07 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2016.00424 [doi]
PST - epublish
SO  - Front Neurosci. 2016 Sep 21;10:424. doi: 10.3389/fnins.2016.00424. eCollection 
      2016.