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

Abstract

The spontaneously hypertensive rat (SHR) has been proposed as an animal model for Attention-Deficit Hyperactivity Disorder (ADHD). The behavioural 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 investigated whether there are regional differences in dopamine (DA) and acetylcholine (ACh) release and DA D 2-receptor function in SHR compared to their normotensive Wistar-Kyoto (WKY) controls. The DA D 2-receptor agonist, quinpirole, caused significantly greater inhibition of DA release from caudate-putamen but not from nucleus accumbens or prefrontal cortex slices of SHR relative to WKY. DA D 2-receptor blockade by the antagonist, sulpiride, caused a significantly greater increase in DA release from nucleus accumbens slices of SHR compared to WKY suggesting increased efficacy of DA autoreceptors at low endogenous agonist concentrations in the nucleus accumbens of SHR. The electrically-stimulated release of DA was significantly lower in caudate-putamen and prefrontal cortex slices of SHR than in slices of WKY. This could be attributed to increased autoreceptor-mediated inhibition of DA release in caudate-putamen slices but not in the prefrontal cortex. No difference was observed between SHR and WKY with respect to DA D 2-receptor-mediated inhibition of ACh release from caudate-putamen or nucleus accumbens slices, suggesting that postsynaptic DA D 2-receptor function is not altered in SHR relative to WKY.