Journal article
Postnatal hypoxia evokes persistent changes within the male rat's dopaminergic system
Sleep & breathing, Vol.22(2), pp.547-554
05/2018
DOI: 10.1007/s11325-017-1558-6
PMID: 28828549
Abstract
Hypoxic insults occurring during the perinatal period remain the leading cause of permanent brain impairment. Severe cognitive and motor dysfunction, as seen in cerebral palsy, will occur in 4-10% of post-hypoxic newborns. Subtle cognitive impairment, apparent in disorders of minimal brain dysfunction will occur in > 3 million post-hypoxic newborns. Analyses of post-hypoxic rodent brains reveal reduced extracellular levels of dopamine, a key neurotransmitter of vigilance, execute function, and behavior. The purpose of this study was to assess whether synaptic levels of dopamine could be enhanced in post-hypoxic, hypodopaminergic rats.
Newborn male rats were exposed to subtle, repetitive hypoxic insults for 4-6 h per day, during postnatal days 7-11. During adolescence, we quantified dopamine content within the caudate nuclei. We then determined whether extracellular dopamine levels could be increased by injecting the psychostimulant d-amphetamine. We next assessed whether the post-hypoxic rat's response to d-amphetamine would differentially impact place preference behavior when compared with littermate controls.
Total tissue content of dopamine was significantly higher in post-hypoxic rats. Injection of d-amphetamine liberated that dopamine which subsequently enhanced extracellular levels. Post-hypoxic rats acquired conditioned place preference for d-amphetamine during the training days. During the testing day, total time spent in the amphetamine-pairing box did not differ between post-hypoxic and control littermates.
Postnatally occurring hypoxic insults promote remodeling of the dopaminergic system resulting in increased intracellular sequestering of this monoamine. That sequestered dopamine can be released using the psychostimulant d-amphetamine, which did not promote a conditioned place preference any greater than was observed in non-hypoxic littermate controls.
Details
- Title: Subtitle
- Postnatal hypoxia evokes persistent changes within the male rat's dopaminergic system
- Creators
- Michael J Decker - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA. mdecker01@gmail.comKarra A Jones - Department of Pathology, Carver College of Medicine, Iowa City, IA, USAGlenda L Keating - Department of Neurology, Emory University, Atlanta, GA, USADavid B Rye - Department of Neurology, Emory University, Atlanta, GA, USA
- Resource Type
- Journal article
- Publication Details
- Sleep & breathing, Vol.22(2), pp.547-554
- Publisher
- Germany
- DOI
- 10.1007/s11325-017-1558-6
- PMID
- 28828549
- ISSN
- 1520-9512
- eISSN
- 1522-1709
- Grant note
- NS-36695 / NINDS NIH HHS HL72722 / NHLBI NIH HHS NS-40221 / NINDS NIH HHS
- Language
- English
- Date published
- 05/2018
- Academic Unit
- Pathology
- Record Identifier
- 9984047625802771
Metrics
8 Record Views