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In rats with unilateral 6-hydroxydopamine lesions in the nigrostriatal pathway, injection of angiotensin II (2 nmol) into the unlesioned striatum elicited dose-related tight rotations ipsilateral to the lesion. This rotation was suppressed by coadministration of the angiotensin AT1 receptor antagonist, losartan (2 nmol), which had no significant effect when injected alone. Preadministration of the dopamine antagonist, haloperidol (2 mg/kg i.p.) completely blocked angiotensin II-induced turning at doses of 0.3-3 nmol, and partially at 10 nmol. These results further confirm the hypothesis that Ang II is intrinsically involved in modulating dopamine release in the striatum, an effect which is mediated predominantly by AT1 receptors. |
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