Email updates

Keep up to date with the latest news and content from BMC Pharmacology and BioMed Central.

Open Access Highly Accessed Research article

The effect of GABA receptor ligands in experimental spina bifida occulta

Wayne Briner

Author Affiliations

Department of Psychology, University of Nebraska at Kearney Kearney, NE, 68849, USA

BMC Pharmacology 2001, 1:2  doi:10.1186/1471-2210-1-2

Published: 15 August 2001

Abstract

Background

The pathophysiology behind spina bifida and other neural tube defects (NTDs) is unclear. Folic acid is one variable, but other factors remain. Studies suggest that substances active at the GABA receptor may produce NTDs. To test this hypothesis pregnant rats were exposed to either the GABA a agonist muscimol (1, 2 or 4 mg/kg), the GABA a antagonist bicuculline (.5, 1, or 2 mg/kg), the GABA b agonist baclofen (15, 30, 60 mg/kg), or the GABA b antagonist hydroxysaclofen (1, 3, or 5 mg/kg) during neural tube formation. Normal saline was used as a control and valproic acid (600 mg/kg) as a positive control. The embryos were analyzed for the presence of a spina bifida like NTD.

Results

After drug administration the pregnancies were allowed to proceed to the 21st day of gestation. Then embryos were removed and skeletons staining and cleared. Vertebral arch closure was measured. Results indicate that the GABAa receptor agonist muscimol, the GABAa receptor antagonist bicuculline, and the GABAb agonist baclofen produced NTDs characterized by widening of the vertebral arch. Oppositely the GABAb antagonist hydroxysaclofen produced narrowing of the vertebral arches.

Conclusions

The findings indicate that GABA a or b ligands are capable of altering neural formation. GABA may play a greater than appreciated role in neural tube formation and may be important in NTDs. The narrowing of the vertebral arch produced by the GABA b antagonist hydroxysalcofen suggests that GABA b receptor may play an undefined role in neural tube closure that differs from the GABA a receptor.