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 tachykinin (TK) NK-3 receptor agonist [Asp5,6,MePhe8]substance P(5-11), also referred to as amino-senktide (NH2-SENK), markedly reduced alcohol 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 following administration into the lateral ventricle. Injection of NH2-SENK, 25 ng/site, in the NBM did not modify water or food intake in water deprived rats, providing evidence for the behavioral selectivity of the effect on ethanol intake. The selective TK NK-3 receptor antagonist, R-820, injected in the NBM at the dose of 1000 ng/site 5 min before NH2-SENK 5 ng/site, significantly reduced the effect of NH2-SENK. The selective TK NK-1 receptor agonist [Sar9,Met(O2)11]substance P inhibited alcohol intake following injection in the NBM only at 25 ng/site; but the same dose induced marked grooming and inhibited also water intake in water deprived rats. The present results confirm that TK NK-3, but not NK-1, receptor agonists selectively inhibit ethanol intake in alcohol-preferring rats and suggest that the NBM is a site of action for their effect.
Ciccocioppo
R
R
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Italy.
Panocka
I
I
Polidori
C
C
De Caro
G
G
Regoli
D
D
Massi
M
M
D000428:Alcohol Drinking; D000704:Analysis of Variance; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D018042:Receptors, Neurokinin-3 / Q000187:drug effects*; D013268:Stimulation, Chemical; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013377:Substantia Innominata / Q000187:drug effects*
D007211:Indoles; D009842:Oligopeptides; D010446:Peptide Fragments; C109443:R 820; D018040:Receptors, Neurokinin-1; D018042:Receptors, Neurokinin-3; C057852:substance P (5-11), Asp(5,6)-MePhe(8)-; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P