Korean J Physiol Pharmacol.  2007 Jun;11(3):113-119.

Developmental Disability Animal Model Based on Neonatal Lipopolysaccharide with Altered 5-HT Function

Affiliations
  • 1Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea.
  • 2Department of Diagnostic Radiology, Brain Korea 21 Project for Medical Sciences, Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea.
  • 3Department of Pharmacology, Wonkwang University College of Medicine, Iksan 570-749, Korea.

Abstract

Developmental disability shows life-long behavioral abnormality with no significant physical malformation. This study was undertaken to develop an animal model for developmental disability by using two-factor approach. Lipopolysaccharide (LPS), a bacterial toxin, and NAN-190, a 5-HT1A receptor antagonist, were administered to Sprague-Dawley rats on postnatal day (PND) 5 to induce inflammation and an altered 5-HT system, respectively. Long-term alteration of behavior occurred in the drug-treated groups. The LPS-treated group showed impaired motor coordination in the Rota-rod test. The LPS- treated or both LPS and NAN-190-treated groups showed impaired fore-paw muscle power in the wire maneuver test. These groups also showed decreased white matter volume and increased serotonergic fibers. The LPS and NAN-190-treated group also exhibited neurologic deficit in the placing reaction test and impaired equilibrium function in the tilt table test. The results showed that a variety of altered behaviors can be generated by two factor model, and suggested that combination of important etiologic factors and possible underlying defects is a promising strategy of establishing an animal model for developmental disabilities.

Keyword

Developmental disability; Lipopolysaccharide; 5-HT1A receptor; Animal model

MeSH Terms

Animals*
Developmental Disabilities*
Inflammation
Models, Animal*
Neurologic Manifestations
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A
Serotonin*
Tilt-Table Test
Receptor, Serotonin, 5-HT1A
Serotonin
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