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Postnatal hypoxia evokes persistent changes within the male rat's dopaminergic system
Michael J Decker1,2,3, Karra A Jones4, Glenda L Keating5
1School of Nursing, Case Western Reserve University, Cleveland, OH, USA. mdecker01@gmail.com.
Insights
Perinatal hypoxia increases dopamine storage in the brain. Psychostimulant administration can release this dopamine, potentially aiding cognitive function recovery in affected newborns.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Neuropharmacology
Background:
- Perinatal hypoxic insults are a primary cause of permanent brain damage in newborns.
- Hypoxia can lead to severe (e.g., cerebral palsy) and subtle (e.g., minimal brain dysfunction) cognitive and motor impairments.
- Reduced extracellular dopamine, a neurotransmitter crucial for vigilance and executive function, is observed in post-hypoxic rodent brains.
Purpose of the Study:
- To investigate whether synaptic dopamine levels can be elevated in rats subjected to perinatal hypoxic insults.
- To explore the potential of psychostimulants to restore dopaminergic function following neonatal hypoxia.
Main Methods:
- Newborn male rats were exposed to repetitive hypoxic insults during early postnatal development.
- Dopamine levels in the caudate nuclei were quantified during adolescence.
- The effect of d-amphetamine administration on extracellular dopamine and place preference behavior was assessed.
Main Results:
- Post-hypoxic rats exhibited significantly higher total dopamine content in brain tissue.
- D-amphetamine injection successfully released sequestered dopamine, increasing extracellular levels.
- While post-hypoxic rats showed place preference for d-amphetamine during training, no difference was observed during testing compared to controls.
Conclusions:
- Neonatal hypoxia induces remodeling of the dopaminergic system, leading to increased intracellular dopamine storage.
- The psychostimulant d-amphetamine can effectively release this sequestered dopamine.
- This dopamine release did not result in a greater conditioned place preference compared to non-hypoxic controls, suggesting complex behavioral effects.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
