ALPHA(2)-ADRENOCEPTOR MEDIATED INHIBITION OF [H-3] DOPAMINE RELEASE FROM NUCLEUS-ACCUMBENS SLICES AND MONOAMINE LEVELS IN A RAT MODEL FOR ATTENTION-DEFICIT HYPERACTIVITY DISORDER

The spontaneously hypertensive rat (SHR) has been proposed as an anima l model for attention-deficit hyperactivity disorder (ADHD). The behav ioural problems have been suggested to be secondary to altered reinfor cement mechanisms in which nucleus accumbens dopaminergic activity pla ys an important role. Interaction between the noradrenergic and dopami nergic system in the nucleus accumbens has been implicated in the loco motor hyperactivity and impaired discriminative performance of SHR. Th e present study therefore investigated whether there was any change in the alpha(2)-adrenoceptor mediated inhibition of dopamine release fro m nucleus accumbens slices of SHR in comparison with their normotensiv e Wistar-Kyoto (WKY) controls. The electrically stimulated release of [H-3]dopamine (DA) from nucleus accumbens slices was decreased to a si milar extent by UK14,304, an alpha(2)-adrenoceptor agonist, in SHR and WKY. Basal norepinephrine (NE) levels were increased in locus coerule us (LC) and A(2) noradrenergic nuclei, but not in the A(2) nucleus of SHR, while basal serotonin (5-HT) levels were increased in all these p ons-medulla nuclei. These results suggest that a primarily dysfunction al LC and A(2) nucleus does not have a secondary effect on dopaminergi c transmission in the nucleus accumbens via alpha(2)-adrenoceptor medi ated inhibition of DA release. Basal monoamine levels in several brain areas of SHR were significantly different from that of WKY. DA, and 5 -HT turnover were decreased in SHR versus WKY suggesting hypofunctiona l dopaminergic and serotonergic systems in some barin areas of SHR.