Antidiuretic effects of oxotremorine microinjected into the hypothalamic supraoptic and paraventricular nuclei in a water-loaded and ethanol-anesthetized rat.

The effect of oxotremorine, a muscarinic agonist, on urine outflow compared with the effects of other cholinergic agonists and inhibitory effects of cholinergic antagonists upon the cholinergic actions were studied by microinjecting drugs stereotaxically, unilaterally into the supraoptic (SON) or paraventricular nuclei (PVN) in the hypothalamus of the rat which was loaded with water and anesthetized with ethanol. Oxotremorine decreased the urine outflow in dose- and time-dependent manners when microinjected into these nuclei. The median effective doses (ED50) were approx. 0.3 and 0.2 nmol in SON an PVN, respectively, being much less than ED50 values for nicotine. The time course of the antidiuretic effects was relatively slow, with the minimal urine outflow at approx. 30 min and the duration of one or longer hours. The antidiuretic effects of oxotremorine in these nuclei as well as the effects of acetylcholine and nicotine were completely blocked by pretreatment with atropine. The pretreatment with hexamethonium inhibited partially the effects of nicotine, but was unable to inhibit the effects of oxotremorine and acetylcholine. The data suggest that the antidiuretic effects of cholinergic agonists in SON and PVN are predominantly mediated through a muscarinic type of acetylcholine receptor. A possible mechanism for the antidiuretic effects is discussed.