Up-regulation of dopamine receptors in the brain of the spontaneously hypertensive rat: an autoradiographic analysis

Abstract

Recent evidence points to a dysfunction of brain dopaminergic mechanisms in the spontaneously hypertensive rat. Using in vitro receptor autoradiography, we assessed the density of D1 and D2 dopamine receptors in the brain of spontaneously hypertensive rats and their normotensive controls the Wistar-Kyoto rat. Brain sections from five- and 15-week-old rats were incubated with 1 nM [3H]SCH 23390 (D1 receptor antagonist) or 15 nM [3H]sulpiride (D2 receptor antagonist), and exposed along with radioactive standards to 3H-Hyperfilm. The binding density of selected brain regions (anteromedial prefrontal cortex, cingulate cortex, lateral septal nucleus, nucleus accumbens, caudate-putamen, globus pallidus, amygdaloid complex) were quantified using computer-assisted densitometry. These experiments showed a significant increase in the binding density of [3H]SCH 23390 in the nucleus accumbens and caudate-putamen of five- and 15-week-old spontaneously hypertensive rats. The binding density of [3H]SCH 23390 was increased in the lateral septal nucleus of five-week-old and globus pallidus of 15-week-old spontaneously hypertensive rats. The binding density of [3H]sulpiride was also greater in the nucleus accumbens of five-week-old spontaneously hypertensive rats. The present investigation demonstrates an up-regulation of D1 dopamine receptors in spontaneously hypertensive rats with established hypertension. More importantly, up-regulation of D1 and D2 dopamine receptors in the striatum of young prehypertensive spontaneously hypertensive rats suggests that dopamine may be involved in the pathogenesis of hypertension in this strain of genetically hypertensive rats.