Chronic neonatal diazoxide therapy is not associated with adverse effects

Michele M. Cox, Christopher C. Wendler, Ildiko Erdelyi, Amanda P. Beck, Caroline Zeiss, Scott A. Rivkees

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalOnLine Journal of Biological Sciences
Volume14
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

diazoxide
Diazoxide
adverse effects
therapeutics
Brain
Therapeutics
mice
brain
pups
Phenotype
phenotype
KATP Channels
neuroprotective effect
potassium channels
Testing
Neuroprotective Agents
Locomotion
reflexes
agonists
Visual Acuity

Keywords

  • Behavior
  • Depression
  • Diazoxide
  • Forced swim

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chronic neonatal diazoxide therapy is not associated with adverse effects. / Cox, Michele M.; Wendler, Christopher C.; Erdelyi, Ildiko; Beck, Amanda P.; Zeiss, Caroline; Rivkees, Scott A.

In: OnLine Journal of Biological Sciences, Vol. 14, No. 1, 2014, p. 49-56.

Research output: Contribution to journalArticle

Cox, Michele M. ; Wendler, Christopher C. ; Erdelyi, Ildiko ; Beck, Amanda P. ; Zeiss, Caroline ; Rivkees, Scott A. / Chronic neonatal diazoxide therapy is not associated with adverse effects. In: OnLine Journal of Biological Sciences. 2014 ; Vol. 14, No. 1. pp. 49-56.
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