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Genetically determined differences in noradrenergic function: The spontaneously hypertensive rat model.

Toni-Lee Sterley1, Fleur M Howells2, Vivienne A Russell1

  • 1Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.

Brain Research
|November 28, 2015
PubMed
Summary
This summary is machine-generated.

Early life stress, like maternal separation, alters norepinephrine release in the hippocampus of spontaneously hypertensive rats (SHRs), a genetic model for attention-deficit/hyperactivity disorder (ADHD), impacting noradrenergic function differently than in control rats.

Keywords:
ADHDGABAMaternal separationNMDASHRWKY

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Area of Science:

  • Neuroscience
  • Behavioral Genetics
  • Pharmacology

Background:

  • Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic component, but the influence of early life stress on its development is not fully understood.
  • The spontaneously hypertensive rat (SHR) is a widely used genetic model exhibiting ADHD-like behaviors and known noradrenergic system disturbances.
  • Previous research indicated maternal separation did not induce anxiety-like behaviors in SHR, unlike in control rat strains.

Purpose of the Study:

  • To investigate the impact of maternal separation on approach behavior in preadolescent SHR and Wistar-Kyoto (WKY) rats.
  • To determine if maternal separation alters GABAA and NMDA receptor-mediated regulation of norepinephrine release in the hippocampus of SHR and WKY rats.

Main Methods:

  • Maternal separation was performed on SHR and WKY rat pups.
  • Approach behavior was assessed in response to a novel object.
  • GABAA and NMDA receptor-mediated regulation of norepinephrine release in hippocampal tissue was measured.

Main Results:

  • Maternal separation increased GABAA receptor-mediated inhibition of norepinephrine release in both male and female SHR hippocampus, but not in WKY rats.
  • Maternal separation differentially affected NMDA receptor-mediated inhibition of norepinephrine release, increasing it in SHR but not WKY rats.
  • Exploratory activity was higher in female SHR compared to WKY rats, irrespective of maternal separation.

Conclusions:

  • Early life stress through maternal separation significantly alters noradrenergic function in the SHR hippocampus in both sexes.
  • GABA and glutamate regulation of norepinephrine release in the hippocampus is uniquely affected by maternal separation in the SHR model.
  • These findings highlight the complex interplay between genetic predisposition and early life stress in modulating neurochemical systems relevant to ADHD.