DRUGS ACTING AT CENTRAL BENZODIAZEPINE RECEPTORS ATTENUATE ETHANOL-INDUCED GASTRIC-LESIONS IN RATS

The characteristics of the receptors involved in the protective action of benzodiazepines against ethanol-induced gastric lesions were inves tigated by studying the effect of benzodiazepine ligands on such lesio ns in both intact and unilaterally vagotomized rats. Clonazepam )-1,3- dihydro-7-nitro-2H-1,4-benzodiazepine-2-one] a specific central-type r eceptor agonist (0.625-2.5 mg/kg p.o. or i.p.) and CGS 9896 yl)-2,5-di hydropyrazolo(4,3-c)quinoline-3(3H)-one] a non-sedative partial agonis t with anxiolytic properties (2.5-10 mg/kg p.o.) significantly reduced the gastric damage induced by ethanol (10 ml/kg of a 50% solution v/v p.o.) in non-vagotomized rats but Ro 5-4864 -1,3-dihydro-1-methyl-2H- 1,4-benzodiazepine-2-one] a pure peripheral-type receptor agonist (5-2 0 mg/kg p.o.) failed to affect this damage. The protective action of c lonazepam and CGS 9896 against ethanol-induced gastric lesions was blo cked, dose dependently, by the central-type receptor antagonist, fluma zenil [ethyl 6-oxo-4H-imidazo(1,4)benzodiazepine-3-carboxylate] (1.25- 20 mg/kg i.p.). In the unilaterally vagotomized rat, ethanol produced lesions in the right (vagotomized) and the left (non-vagotomized) halv es of the gastric mucosa to nearly the same extent, while clonazepam a nd CGS 9896 uniformly decreased the lesions in both halves. It is conc luded that central-type benzodiazepine receptors located in the stomac h, specifically those mediating the anxiolytic effect of benzodiazepin es, are involved in the protective action of benzodiazepines against e thanol-induced gastric lesions.