STIMULATION OF TACHYKININ NK-3 RECEPTORS IN THE NUCLEUS BASALIS MAGNOCELLULARIS REDUCES ALCOHOL INTAKE IN RATS

Injections in the nucleus basalis magnocellularis (NBM) of the tachyki nin (TK) NK-3 receptor agonist [Asp(5,6),MePhe(8)]substance P(5-11) ), also referred to as amino-senktide (NH2-SENK), markedly reduced alcoh ol intake in genetically selected alcohol-preferring rats, offered 10% ethanol 2 h/day. The threshold dose in the NBM was 0.5 ng/site, while neither 1 nor 10 ng/rat of NH2-SENK inhibited alcohol intake followin g administration into the lateral ventricle. Injection of NH2-SENK, 25 ng/site, in the NBM did not modify water or food intake in water depr ived rats, providing evidence for the behavioral selectivity of the ef fect on ethanol intake. The selective TK NK-3 receptor antagonist, R-8 20, injected in the NBM at the dose of 1000 ng/site 5 min before NH2-S ENK 5 ng/site, significantly reduced the effect of NH2-SENK. The selec tive TK NK-1 receptor agonist [Sar(9),Met(O-2)(11)]substance P inhibit ed alcohol intake following injection in the NBM only at 25 ng/site; b ut the same dose induced marked grooming and inhibited also water inta ke in water deprived rats. The present results confirm that TK NK-3, b ut not NK-1, receptor agonists selectively inhibit ethanol intake in a lcohol-preferring rats and suggest that the NBM is a site of action fo r their effect. (C) 1997 Elsevier Science Inc.