The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention-deficit hyperactivity disorder (ADHD). The behavioural problems have been suggested to be secondary to altered reinforcement mechanisms in which nucleus accumbens dopaminergic activity plays an important role. Interaction between the noradrenergic and dopaminergic system in the nucleus accumbens has been implicated in the locomotor hyperactivity and impaired discriminative performance of SHR. The present study therefore investigated whether there was any change in the alpha 2-adrenoceptor mediated inhibition of dopamine release from nucleus accumbens slices of SHR in comparison with their normotensive Wistar-Kyoto (WKY) controls. The electrically stimulated release of [3H]dopamine (DA) from nucleus accumbens slices was decreased to a similar extent by UK14,304, an alpha 2-adrenoceptor agonist, in SHR and WKY. Basal norepinephrine (NE) levels were increased in locus coeruleus (LC) and A2 noradrenergic nuclei, but not in the A1 nucleus of SHR, while basal serotonin (5-HT) levels were increased in all these pons-medulla nuclei. These results suggest that a primarily dysfunctional LC and A2 nucleus does not have a secondary effect on dopaminergic transmission in the nucleus accumbens via alpha 2-adrenoceptor mediated 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 hypofunctional dopaminergic and serotonergic systems in some brain areas of SHR.

Effects of DSP-4 on noradrenaline (NA), 3-methoxy-4-hydroxyphenyl glycol (MHPG), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) levels and on beta adrenoceptor binding kinetics (Bmax and KD) in rat hippocampus, cortex and hypothalamus were studied between 24 hours and 14 days after systemic administration. Beta adrenoceptor numbers in hippocampus and cortex, but not in hypothalamus, were significantly increased after DSP-4. No significant changes in KD values were observed in hypothalamus, but significant increases in this parameter were measured in hippocampus and cortex. NA and MHPG levels were significantly decreased in all three brain regions, but MHPG/NA ratios were increased in hippocampus, decreased in cortex and unchanged in hypothalamus. Very prominent increases in 5-HIAA levels were observed in all three brain regions, but only at one day after DSP-4. The greatest increases in 5-HIAA levels occurred in the hippocampus, but this effect of DSP-4 appeared to be slightly diminished by pre-treatment with fluoxetine. In cortex and hippocampus 5-HT levels were slightly, but significantly decreased after DSP-4.

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