SELECTIVE AGONISTS AT NK3 TACHYKININ RECEPTORS INHIBIT ALCOHOL INTAKEIN SARDINIAN ALCOHOL-PREFERRING RATS

The present study evaluated the effect of tachykinin agonists, selecti ve for different neurokinin (NK) receptors, on alcohol intake in genet ically selected, Sardinian alcohol-preferring rats. Tachykinins were g iven by intracerebroventricular injection just before access to fluids . In rats offered both water and 8% ethanol 2 h/day, the NK3 selective agonists [Asp(5,6),MePhe(8)]substance P(5-11), Suc-[Asp(6),MePhe(8)]s ubstance P(6-11), and [MePhe(7)]neurokinin B markedly suppressed alcoh ol intake. The NK1 selective agonist [Sar(9),Met(O-2)11]substance P an d the NK2 selective agonist GR 64349 did not reduce alcohol intake. At doses that inhibited alcohol intake, the NK3 agonists did not modify water intake; total fluid intake was significantly reduced only follow ing 500 ng/rat of [Asp(5,6),MePhe(8)]substance P(5-11). When rats were given a longer access to fluids (8% alcohol for 2 h, but water for 4 h), again, NK3 agonists suppressed alcohol intake, but not total fluid intake. Moreover, NK3 agonists did not modify solid food intake in fo od-deprived rats, nor water intake in water-deprived rats, when alcoho l was not available. These findings indicate that NK3 agonists inhibit alcohol intake in Sardinian alcohol-preferring rats and that their ef fect is behaviorally selective. They also suggest that central NK3 rec eptors may be involved in alcohol intake control in rats.