ALTERED DOPAMINERGIC FUNCTION IN THE PREFRONTAL CORTEX, NUCLEUS-ACCUMBENS AND CAUDATE-PUTAMEN OF AN ANIMAL-MODEL OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER - THE SPONTANEOUSLY HYPERTENSIVE RAT

The spontaneously hypertensive rat (SHR) has been proposed as an anima l model for Attention-Deficit Hyperactivity Disorder (ADHD). The behav ioural problems of ADHD have been suggested to be secondary to altered reinforcement mechanisms resulting from dysfunction of the mesolimbic and mesocortical dopaminergic systems. The present study therefore in vestigated whether there are regional differences in dopamine (DA) and acetylcholine (ACh) release and DA D-2-receptor function in SHR compa red to their normotensive Wistar-Kyoto (WKY) controls. The DA D-2-rece ptor agonist, quinpirole, caused significantly greater inhibition of D A release from caudate-putamen but not from nucleus accumbens or prefr ontal cortex slices of SHR relative to WKY. DA D-2-receptor blockade b y the antagonist, sulpiride, caused a significantly greater increase i n DA release from nucleus accumbens slices of SHR compared to WKY sugg esting increased efficacy of DA autoreceptors at low endogenous agonis t concentrations in the nucleus accumbens of SHR. The electrically-sti mulated release of DA was significantly lower in caudate-putamen acid prefrontal cortex slices of SHR than in slices of WKY. This could be a ttributed to increased autoreceptor-mediated inhibition of DA release in caudate-putamen slices but not in the prefrontal cortex. No differe nce was observed between SHR and WKY with respect to DA D-2-receptor-m ediated inhibition of ACh release from caudate-putamen or nucleus accu mbens slices, suggesting that postsynaptic DA D-2-receptor function is not altered in SHR relative to WKY.