Increased glutamate-stimulated norepinephrine release from prefrontal cortex slices of spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) have behavioral characteristics (hype ractivity, impulsiveness, poorly sustained attention) similar to the behavi oral disturbances of children with attention-deficit hyperactivity disorder (ADHD). We have previously shown that dopaminergic and noradrenergic syste ms are disturbed in the prefrontal cortex of SHR compared to their normoten sive Wistar-Kyoto (WKY) control rats. It was of interest to determine wheth er 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-dep endent stimulation of [H-3]norepinephrine release from rat prefrontal corte x slices. Glutamate (100 muM and 1 mM) caused significantly greater release of norepinephrine from prefrontal cortex slices of SHR than from control s lices. The effect of glutamate was not mediated by NMDA receptors, since NM DA (10 and 100 muM) did not exert any effect on norepinephrine release and MK-801 (10 muM) did not antagonize the effect of 100 muM glutamate. These r esults demonstrate that glutamate stimulates norepinephrine release from ra t prefrontal cortex slices and that this increase is enhanced in SHR. The r esults are consistent with the suggestion that the noradrenergic system is overactive in prefrontal cortex of SHR, the animal model for ADHD.