Pharmacologic independence of subfornical organ receptors mediating drinking

In rats with chronically implanted cannulae in the subfornical organ (SFO), the relationship between cholinergic- and angiotensin (AII)-induced drinking was investigated pharmacologically. All substances were injected via SFO cannulae which did not rupture ventricular ependyma. Pretreatment with low doses of the muscarinic antagonist atropine abolished carbachol-induced drinking, while nicotinic antagonists had no effect. Nonetheless, pretreatment with much larger doses of atropine had no effect on AII-induced drinking. Similarly, relatively small doses of the AII antagonist, saralasin, blocked AII-induced drinking, yet a much larger dose of saralasin had no effect on carbachol-induced drinking. The receptors mediating cholinergic- and AII-induced drinking therefore cannot be in series and must be in parallel. A hypothesis is proposed to account for this independence and for the significance of the SFO cholinergic innervation.