title: Central effects of nafadotride, a dopamine D3 receptor antagonist, in rats. Comparison with haloperidol and clozapine.
abstract: The aim of this study was to examine behavioral and biochemical effects of nafadotride, the new dopamine D3 receptor antagonist, and to compare it with haloperidol (dopamine D2 receptor antagonist) and clozapine (predominate dopamine D4 receptor antagonist). Each drug was injected to adult male Wistar rats intraperitoneally, each at a single dose and for 14 consecutive days. Thirty minutes after single or last injection of the examined drugs, the following behavioral parameters were recorded: yawning, oral activity, locomotion, exploratory activity, catalepsy and coordination ability. By HPLC/ED methods, we determined the effects of the examined antagonists on the levels of biogenic amines in striatum and hippocampus: dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA). Additionally, DA and 5-HT synthesis rate was determined in striatum and 5-HT in hippocampus. The results of the study indicate that nafadotride, the dopamine D3 receptor antagonist, has a behavioral and biochemical profile of action different from that of haloperidol but partially similar to that of clozapine.
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Jordana 38, PL 41-808 Zabrze, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kuballa
authors.forename: Przemysław
authors.initials: P
authors.lastname: Nowak
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Labus
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bortel
authors.forename: Joanna
authors.initials: J
authors.lastname: Dabrowska
authors.forename: Marek
authors.initials: M
authors.lastname: Swoboda
authors.forename: Adam
authors.initials: A
authors.lastname: Kwieciński
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kostrzewa
authors.forename: Ryszard
authors.initials: R
authors.lastname: Brus
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*
chemical_list: D001679:Biogenic Amines; D009281:Naphthalenes; D011759:Pyrrolidines; D050637:Receptors, Dopamine D3; D007980:Levodopa; D006916:5-Hydroxytryptophan; D003024:Clozapine; D006220:Haloperidol; C097285:nafadotride