Abnormality of circadian rhythm accompanied by an increase in frontal cortex serotonin in animal model of autism

Neurosci Res. 2007 Feb;57(2):289-95. doi: 10.1016/j.neures.2006.10.018. Epub 2006 Dec 6.


Several clinical reports have indicated that autistic patients often show disturbance of the circadian rhythm, which may be related to dysfunction of the serotonergic system in the brain. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we examined locomotor activity and feeding under a reversed 12-h light/dark cycle, and found disturbance of the circadian rhythm characterized by frequent arousal during the light/sleep phase. In addition, measurement of brain serotonin (5-HT) level using in vivo microdialysis showed that the brain 5-HT level in VPA-exposed rats was significantly higher than that in control rats. These results suggest that a higher brain 5-HT level might be responsible for the irregular sleep/awake rhythm in autism.

MeSH terms

  • Animals
  • Animals, Newborn
  • Autistic Disorder / complications*
  • Autistic Disorder / pathology*
  • Behavior, Animal
  • Chronobiology Disorders / etiology*
  • Disease Models, Animal
  • Exploratory Behavior / physiology
  • Female
  • Frontal Lobe / metabolism*
  • Gene Expression Regulation
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Serotonin / metabolism*
  • Valproic Acid


  • Serotonin
  • Valproic Acid