Central administration of benzodiazepines alters water absorption by the rat ileum in vivo

Abstract

Two types of benzodiazepine receptors have been identified in the central nervous system. The aim of these experiments was to determine if ligands for these receptors alter basal water absorption by rat ileum in vivo after central administration. Specifically, the effects on net water flux of the systemic and central administration of diazepam and the central administration of RO 5-4864, a “peripheral” receptor agonist, and of the “central” receptor agonists clonazepam and lorazepam were determined. Diazepam increased absorption at 4.3 mg/250 g body wt i.p. but not at 430 μg/250 g body wt. Intracerebroventricular diazepam (28 μg) increased water absorption. Larger doses had a greater effect. Intracerebroventricular RO 5-4864 (100 μg) increased net water absorption; intracerebroventricular lorazepam (50 or 100 μg) or clonazepam (100 μg) reduced basal water absorption. Systemic atropine (2 mg/kg i.v.) abolished the effect of lorazepam (100 μg i.c.v.). To evaluate the possibility that diazepam and RO 5-4864 have effects similar to those of calcium channel antagonists, nifedipine, nitrendipine, and diltiazem were administered intracerebroventricularly. The dihydropyridine calcium channel antagonists nifedipine and nitrendipine increased basal water absorption. Diltiazem, a benzothiazepine compound, did not alter basal water absorption. We conclude that the binding of benzodiazepine agonists to receptors located in the central nervous system alters net water absorption by the rat ileum. Agonists of the central benzodiazepine receptor reduce basal water absorption via a cholinergic neural pathway. Peripheral agonists increase net water absorption. In this model, diazepam behaves as a peripheral receptor agonist. This study provides further evidence of a role for the central nervous system in the regulation of intestinal absorption of water and ions.