UP-REGULATION OF ANGIOTENSIN-II AT(1) RECEPTORS IN THE MOUSE NUCLEUS-ACCUMBENS BY CHRONIC HALOPERIDOL TREATMENT

The distribution of angiotensin II AT(1) and AT(2) receptor subtypes w ere mapped in the mouse brain by in vitro autoradiography. Along with a differing distribution of AT(1) and AT(2) receptors in the hind brai n compared to the rat, moderate densities of AT(1) receptors were obse rved in dopamine-rich regions, namely the caudate putamen and nucleus accumbens, previously observed in the human, but not rat or rabbit. Co nsidering our previous anatomical and functional studies demonstrating an interaction between brain angiotensin II and dopaminergic systems, the effect of chronic treatment with the dopamine antagonist, haloper idol, on AT(1) and AT(2) receptor levels was investigated in the mouse brain. Haloperidol treatment for 21 days resulted in an increase in a ngiotensin II AT(1) receptor levels in the nucleus accumbens, accompan ied by an increase in dopamine D-2 receptors, but no change in dopamin e D-1 receptors. Striatal AT(1) receptors did not alter with treatment , nor did AT(1) or AT(2) receptors in a number of brain regions not as sociated with dopaminergic systems, such as the median preoptic nucleu s, paraventricular hypothalamic nucleus, and nucleus of the solitary t ract. The present study suggests that brain angiotensin II-dopamine in teractions extend beyond the known effects on the nigrostriatal dopami nergic system, to the mesocorticolimbic dopaminergic system.