FURTHER EVIDENCE THAT CENTRAL TACHYKININ NK-1 RECEPTORS MEDIATE THE INHIBITORY EFFECT OF TACHYKININS ON ANGIOTENSIN-INDUCED DRINKING IN RATS

The order of potency of tachykinin (TK) receptor agonists suggests tha t TK NK-1 receptors mediate their inhibitory effect on water intake in duced by intracerebroventricular (ICV) injection of angiotensin II (An gII) in rats. The present study was aimed at further evaluating which TK receptor subtype mediates the effect, using selective antagonists f or the TK receptor subtypes. Pulse ICV injection of the TK agonist neu ropeptide gamma (NP gamma), 31-250 ng/rat, markedly inhibited AngII-in duced water intake. The ICV injection of the NK-1 receptor antagonist SR140333, 0.5 mu g/rat, significantly reduced, while 1 mu g/rat comple tely abolished the inhibitory effect of NP gamma, 125 ng/rat. The sele ctive NK-2 receptor antagonist SR48968 and the selective NK-3 receptor antagonist R820 were devoid of any effect up to the ICV dose of 2 mu g/rat. On the other hand, ICV injection of SR140333, 1 mu g/rat, did n ot increase drinking induced by ICV injection of AngII, 0.1-10 ng/rat, and did not increase drinking in water sated or water deprived rats. The results of the present study confirm that central TKergic mechanis ms inhibit AngII-induced drinking in rats, and provide further evidenc e that TK NK-1 receptors mediate the effect. Failure of ICV injected S R 140333 to increase AngII-induced drinking, as well as water intake i n sated or deprived rats suggests that brain NK-I receptor mechanisms apparently do not exert a tonic control on AngII-induced drinking and, in general, on water intake in rats. From a pharmacological point of view, the inhibitory effect of TKs on the dipsogenic action of AngII c an represent a functional test for activity at central NK-1 receptors in rats. (C) 1998 Elsevier Science Inc.