Increased glutamate-stimulated norepinephrine release from prefrontal cortex slices of spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR) have behavioral characteristics (hyperactivity, impulsiveness, poorly sustained attention) similar to the behavioral disturbances of children with attention-deficit hyperactivity disorder (ADHD). We have previously shown that dopaminergic and noradrenergic systems are disturbed in the prefrontal cortex of SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. It was of interest to determine whether the underlying neural circuits that use glutamate as a neurotransmitter function normally in the prefrontal cortex of SHR. An in vitro superfusion technique was used to demonstrate that glutamate caused a concentration-dependent stimulation of [3H]norepinephrine release from rat prefrontal cortex slices. Glutamate (100 microM and 1 mM) caused significantly greater release of norepinephrine from prefrontal cortex slices of SHR than from control slices. The effect of glutamate was not mediated by NMDA receptors, since NMDA (10 and 100 microM) did not exert any effect on norepinephrine release and MK-801 (10 microM) did not antagonize the effect of 100 microM glutamate. These results demonstrate that glutamate stimulates norepinephrine release from rat prefrontal cortex slices and that this increase is enhanced in SHR. The results are consistent with the suggestion that the noradrenergic system is overactive in prefrontal cortex of SHR, the animal model for ADHD.
Russell
V A
VA
Department of Physiology, University of Cape Town, Faculty of Health Sciences, Observatory, South Africa. russell@curie.uct.ac.za
Wiggins
T M
TM
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D007175:Impulsive Behavior / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000493:pharmacokinetics*; D009924:Organ Culture Techniques; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014316:Tritium
D018691:Excitatory Amino Acid Antagonists; D014316:Tritium; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D009638:Norepinephrine