Abstract
1. The ability of angiotensin II to modulate dopamine release from rat striatal slices in vitro and in the intact rat striatum in vivo was assessed by the microdialysis technique. 2. In slices of rat striatum, angiotensin II (0.1-1.0 microM) induced a concentration-related increase in endogenous dopamine release which was maximal (approximately 250% above basal levels) within the first 2-4 min of agonist application and subsequently declined to near basal values. The angiotensin II-induced increase in dopamine release was Ca(2+)-dependent and was completely antagonized by the selective AT1 receptor antagonist, losartan (1.0 microM). In contrast, the AT2 receptor antagonist, PD123177 (1.0 microM) failed to modify the angiotensin II-induced response. Neither antagonist alone modified basal dopamine release from striatal slices. 3. In freely moving rats, angiotensin II (1.0-10 microM; administered via the microdialysis probe) induced a concentration-related increase in extracellular levels of dopamine which was maximal (approximately 150% above basal levels) within 20-40 min of agonist application and subsequently declined. The angiotensin II (10 microM)-induced increase in extracellular levels of dopamine was completely antagonized by the AT1 receptor antagonist, losartan (0.1-1.0 microM; administered via the microdialysis probe) but not by the AT2 receptor antagonist, PD123177 (1.0 microM; administered via the microdialysis probe). Neither antagonist alone modified basal extracellular levels of dopamine. 4. Homogenate radioligand binding studies with [125I]-angiotensin II (0.1 nm) identified relatively low levels of specific binding sites in rat striatal homogenates compared to homogenates of pyriform cortex (51.3 +/- 9.2 and 651.3 +/- 55.1 fmol g-1 wet weight, respectively, mean +/- s.e.mean, n = 3; non-specific binding defined by unlabelled angiotensin II). The majority of the specific [125I]-angiotensin II (0.1 nM) binding in the striatal and pyriform cortex homogenates was sensitive to the selective AT1 receptor antagonist, losartan (1.0 microM). 5. In conclusions the present study provides direct evidence that angiotensin II acting via the AT1 receptor subtype facilitates the release of dopamine in the rat striatum in vitro and in vivo. This receptor-mediated response may account for the modulation of dopamine-mediated behavioural responses by antagonists of the AT1 receptor and inhibitors of angiotensin converting enzyme.