title: Genetically determined differences in noradrenergic function: The spontaneously hypertensive rat model.
abstract: While genetic predisposition is a major factor, it is not known how development of attention-deficit/hyperactivity disorder (ADHD) is modulated by early life stress. The spontaneously hypertensive rat (SHR) displays the behavioral characteristics of ADHD (poorly sustained attention, impulsivity, hyperactivity) and is the most widely studied genetic model of ADHD. We have previously shown that SHR have disturbances in the noradrenergic system and that the early life stress of maternal separation failed to produce anxiety-like behavior in SHR, contrary to control Sprague-Dawley and Wistar-Kyoto (WKY) who showed typical anxiety-like behavior in later life. In the present study we investigated the effect of maternal separation on approach behavior (response to a novel object in a familiar environment) in preadolescent SHR and WKY. We also investigated whether maternal separation altered GABAA and NMDA receptor-mediated regulation of norepinephrine release in preadolescent SHR and WKY hippocampus. We found that female SHR, similar to male SHR, exhibited greater exploratory activity than WKY. Maternal separation significantly increased GABAA receptor-mediated inhibition of glutamate-stimulated release of norepinephrine in male and female SHR hippocampus but had no significant effect in WKY. Maternal separation had opposite effects on NMDA receptor-mediated inhibition of norepinephrine release in SHR and WKY hippocampus, as it increased inhibition of both glutamate-stimulated and depolarization-evoked release in SHR hippocampus but not in WKY. The results of the present study show that noradrenergic function is similarly altered by the early life stress of maternal separation in male and female SHR, while GABA- and glutamate-regulation of norepinephrine release remained unaffected by maternal separation in the control, WKY, rat strain. This article is part of a Special Issue entitled SI: Noradrenergic System.
authors.affiliation: Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.
authors.forename: Toni-Lee
authors.initials: TL
authors.lastname: Sterley
authors.affiliation: Department of Psychiatry, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.
authors.forename: Fleur M
authors.initials: FM
authors.lastname: Howells
authors.affiliation: Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa. Electronic address: vivienne.russell@uct.ac.za.
authors.forename: Vivienne A
authors.initials: VA
authors.lastname: Russell
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011897:Random Allocation; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013045:Species Specificity; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D011188:Potassium; D009638:Norepinephrine; D001640:Bicuculline
keywords: ADHD; GABA; Maternal separation; NMDA; SHR; WKY