Neuropeptide YY5 receptor antagonist CGP71683A: the effects on food intakeand anxiety-related behavior in the rat

The effects of neuropeptide Y Y-5 receptor antagonist (trans-naphtalene-1-s ulphonic acid (4-[(4-amino-quinazolin-2-ylamino)-methyl]cyclohexylmethyl)-a mide hydrochloride; CGP71683A), on food intake, anxiety and locomotor activ ity were studied. CGP71683A (1-10 mg/kg, i.p.) dose-dependently decreased n octurnal and fasting-induced food intake. CGP71683A did not have an anxioge nic-like effect in the rat social interaction test. In the elevated plus-ma ze test, where novel neuropeptide Y Y-1 receptor antagonist (2R)-5-([amino( imino)methyl)amino)-2-[(2,2-diphenylacetyl)-amino-N-[(1R)-1-(4-hydroxypheny l)ethyl-pentanamide (H 409/22) had anxiogenic-like effect, CGP71683A was in active. In the open-field test, carried out immediately after the elevated plus-maze test, CGP71683A inhibited horizontal and vertical activity. CGP71 683A did modify the habituation of locomotor response in novel environment. These data show that the inhibition of food intake induced by CGP71683A co uld not be explained by increased fearfulness, a state that is induced by n europeptide Y Y-1 receptor antagonists. Thus, our data, obtained with first neuropeptide Y Y-5 receptor antagonist CGP71683A, suggest that in contrast to the neuropeptide Y Y-1 receptor, Y-5 receptor is not involved in tonic neuropeptide Y-induced anxiolysis. (C) 2001 Published by Elsevier Science B .V.