The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice.
Bombesin (BN)-like peptides might be involved in the pathogenesis of neuropsychiatric disorders such as schizophrenia. Stereotyped behaviors induced by the dopamine receptor agonist apomorphine or the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine (MK-801) in rodents have been proposed as animal models of schizophrenic psychosis. In the present study we evaluated the effects of the BN/gastrin-releasing peptide receptor (GRP) antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin (6-14) (RC-3095) on apomorphine and MK-801-induced stereotyped behavior in mice. An intraperitoneal (i.p.) injection of RC-3095 (1.0, 10.0 or 100.0 mg/kg) blocked apomorphine-induced stereotypy. The inhibitory effect of RC-3095 on apomorhine-induced stereotypy was similar to that induced by haloperidol (0.5 mg/kg). RC-3095 did not affect stereotyped behavior induced by MK-801 (0.5 mg/kg). The results provide the first evidence that BN/GRP receptor antagonism blocks stereotyped behavior induced by a dopamine agonist. Together with previous evidence, the present study indicates that the BN/GRP receptor can be considered a drug target in the investigation of potential new agents for treating neuropsychiatric disorders.
Meller
Carolina A
CA
Graduate Program in Cellular and Molecular Biology, Center for Biotechnology, Federal University of Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil.
Henriques
João Antônio Pêgas
JA
Schwartsmann
Gilberto
G
Roesler
Rafael
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001058:Apomorphine / Q000008:administration & dosage*; D001839:Bombesin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage*; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D012559:Schizophrenia / Q000139:chemically induced* / Q000188:drug therapy*
D000970:Antineoplastic Agents; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D016291:Dizocilpine Maleate; D001058:Apomorphine; D001839:Bombesin