Increased noradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder--the spontaneously hypertensive rat.
Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit/hyperactivity disorder (ADHD) since SHR are hyperactive and they show defective sustained attention in behavioral tasks. Using an in vitro superfusion technique we showed that norepinephrine (NE) release from prefrontal cortex slices of SHR was not different from that of their Wistar-Kyoto (WKY) control rats when stimulated either electrically or by exposure to buffer containing 25 mM K(+). The monoamine vesicle transporter is, therefore, unlikely to be responsible for the deficiency in DA observed in SHR, since, in contrast to DA, vesicle stores of NE do not appear to be depleted in SHR. In addition, alpha(2)-adrenoceptor mediated inhibition of NE release was reduced in SHR, suggesting that autoreceptor function was deficient in prefrontal cortex of SHR. So, while DA neurotransmission appears to be down-regulated in SHR, the NE system appears to be under less inhibitory control than in WKY suggesting hypodopaminergic and hypernoradrenergic activity in prefrontal cortex of SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between NE and DA systems in the prefrontal cortex, with inhibitory DA activity being decreased and NE activity increased relative to controls.
Russell
V
V
Department of Physiology, Faculty of Health Sciences, Medical School Observatory, University of Cape Town, 7925, Cape Town, South Africa. russell@curie.uct.ac.za
Allie
S
S
Wiggins
T
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism; D019329:Idazoxan / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008959:Models, Neurological; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020318:Rats, Long-Evans; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D004298:Dopamine; D009638:Norepinephrine; D019329:Idazoxan