Neuropeptide Y Y(5) receptor antagonist CGP71683A: the effects on food intake and anxiety-related behavior in the rat.
The effects of neuropeptide Y Y(5) receptor antagonist (trans-naphtalene-1-sulphonic acid [4-[(4-amino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl]-amide hydrochloride; CGP71683A), on food intake, anxiety and locomotor activity were studied. CGP71683A (1-10 mg/kg, i.p.) dose-dependently decreased nocturnal and fasting-induced food intake. CGP71683A did not have an anxiogenic-like effect in the rat social interaction test. In the elevated plus-maze test, where novel neuropeptide Y Y(1) receptor antagonist (2R)-5-([amino(imino)methyl)amino)-2-[(2.2-diphenylacetyl)-amino]-N-[(1R)-1-(4-hydroxyphenyl)ethyl-pentanamide (H 409/22) had anxiogenic-like effect, CGP71683A was inactive. In the open-field test, carried out immediately after the elevated plus-maze test, CGP71683A inhibited horizontal and vertical activity. CGP71683A did modify the habituation of locomotor response in novel environment. These data show that the inhibition of food intake induced by CGP71683A could not be explained by increased fearfulness, a state that is induced by neuropeptide 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.
Department of Pharmacology, University of Tartu, Ravila 19, Tartu 50090, Estonia. Ants.Kask@ut.ee
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Kask
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Vasar
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Heidmets
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Allikmets
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Wikberg
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology
D000577:Amides; C420032:H 409-22; D009281:Naphthalenes; D011743:Pyrimidines; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor; C116786:CGP 71683 A