CHRONIC NEONATAL DIAZOXIDE THERAPY IS NOT ASSOCIATED WITH ADVERSE EFFECTS
Michele M. Cox, Christopher C. Wendler, Ildiko Erdelyi, Amanda Beck, Caroline Zeiss and Scott A. Rivkees
DOI : 10.3844/ojbsci.2014.49.56
OnLine Journal of Biological Sciences
Volume 14, Issue 1
Diazoxide is an ATP-sensitive potassium channel (KATP) agonist that has been shown to neuroprotective effects. These observations raise the possibility that diazoxide may have potential as a therapeutic agent for other applications. This study investigated (1) the long term effects of chronic neonatal administration of diazoxide and (2) the role of KATP on murin behavior and neurohistology. C57B/6J pups were injected daily with diazoxide (10, 20 or 50 mg kg-1) or vehicle from Postnatal days 2 (P2) through P12. Pups were allow to mature and underwent behavioral testing at 5-7 months of age. After behavioral testing, animals were euthanized and morphology of the brains was assessed. No long term adverse effects of neonatal diazoxide therapy on physical characteristics, visual acuity, sensori-motor reflexes, spontaneous locomotor activity, motor coordination/balance or motor learning and memory were observed. In addition, no morphological changes were observed on brains. However, we did observe that diazoxide therapy causes depressive-like phenotypes in female murine mice. Chronic neonatal diazoxide therapy does not cause deficits or enhancements in mice behavior. Diazoxide does not cause abnormal morphological changes in brain anatomy. However, diazoxide does cause gender specific depressive-like phenotype in mice.
© 2014 Michele M. Cox, Christopher C. Wendler, Ildiko Erdelyi, Amanda Beck, Caroline Zeiss and Scott A. Rivkees. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.