Upregulation of angiotensin II AT1 receptors in the mouse nucleus accumbens by chronic haloperidol treatment.
The distribution of angiotensin II AT1 and AT2 receptor subtypes were mapped in the mouse brain by in vitro autoradiography. Along with a differing distribution of AT1 and AT2 receptors in the hind brain compared to the rat, moderate densities of AT1 receptors were observed in dopamine-rich regions, namely the caudate putamen and nucleus accumbens, previously observed in the human, but not rat or rabbit. Considering 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, haloperidol, on AT1 and AT2 receptor levels was investigated in the mouse brain. Haloperidol treatment for 21 days resulted in an increase in angiotensin II AT1 receptor levels in the nucleus accumbens, accompanied by an increase in dopamine D2 receptors, but no change in dopamine D1 receptors. Striatal AT1 receptors did not alter with treatment, nor did AT1 or AT2 receptors in a number of brain regions not associated with dopaminergic systems, such as the median preoptic nucleus, paraventricular hypothalamic nucleus, and nucleus of the solitary tract. The present study suggests that brain angiotensin II-dopamine interactions extend beyond the known effects on the nigrostriatal dopaminergic system, to the mesocorticolimbic dopaminergic system.
Jenkins
T A
TA
Department of Medicine, University of Melbourne, Victoria, Australia.
Chai
S Y
SY
Mendelsohn
F A
FA
D000818:Animals; D001345:Autoradiography; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D015854:Up-Regulation
D018492:Dopamine Antagonists; D011945:Receptors, Angiotensin; D006220:Haloperidol