Increased AMPA receptor function in slices containing the prefrontal cortex of spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR) are used as a genetic model for attention-deficit hyperactivity disorder (ADHD), since they have behavioral characteristics that mimic the major symptoms of ADHD. We have previously shown that dopaminergic and noradrenergic systems are altered in the prefrontal cortex of SHR compared to normotensive Wistar-Kyoto (WKY) control rats. We also showed that neural circuits that use glutamate as a neurotransmitter increased norepinephrine release from rat prefrontal cortex slices and that glutamate caused significantly greater release of norepinephrine from prefrontal cortex slices of SHR than from those of WKY. The effect of glutamate did not appear to be mediated by NMDA receptors, since NMDA did not exert any effect on norepinephrine release and the NMDA receptor antagonist MK-801 did not reduce the effect of glutamate. In this investigation we show that the stimulatory effect of glutamate is greater in SHR than in WKY and that the effect can be antagonised by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The results suggest that glutamatergic neuron terminals in rat prefrontal cortex establish synaptic contacts with noradrenergic terminals to enhance norepinephrine release by activation of AMPA receptors and that this enhancement is amplified in SHR.
Russell
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VA
Department of Human Biology, University of Cape Town, Faculty of Health Sciences., South Atrica. russell@curie.uct.ac.za
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018091:Receptors, AMPA / Q000378:metabolism*
D018091:Receptors, AMPA; D018698:Glutamic Acid; D009638:Norepinephrine