CHRONIC NEONATAL DIAZOXIDE THERAPY IS NOT ASSOCIATED WITH ADVERSE EFFECTS

Abstract

Diazoxide is an ATP-sensitive potassium channel (K_ATP) 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 K_ATP 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.