Peptides 25 (2004) 585–588 Short communication The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice Carolina A. Meller a , João Ant ˆ onio Pˆ egas Henriques a , Gilberto Schwartsmann b , Rafael Roesler a,c,∗ a Graduate Program in Cellular and Molecular Biology, Center for Biotechnology, Federal University of Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil b Department of Internal Medicine, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, and South American Office for Anticancer Drug Development, 90035-003 Porto Alegre, RS, Brazil c Preclinical Neuropharmacology Laboratory, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90046-900 Porto Alegre, RS, Brazil Received 1 October 2003; received in revised form 3 January 2004; accepted 7 January 2004 Available online 10 February 2004 Abstract 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[CH 2 NH]-Leu14) bombesin (6–14) (RC-3095) on apo- morphine 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. © 2004 Elsevier Inc. All rights reserved. Keywords: RC-3095; Bombesin receptor; Gastrin/releasing peptide; Stereotypy; Antipsychotics; Psychosis; Mice 1. Introduction Bombesin (BN)-like peptides such as the mammalian BN counterpart, gastrin releasing peptide (GRP) are distributed throughout the mammalian central nervous system (CNS) and regulate several aspects of CNS function, including feeding, satiety, aversion, reward, anxiety, as well as learn- ing and memory processes [3,8,16,18,20]. The evidence that BN-like peptides are also involved in the pathogenesis of several types of human cancer has led to the development of BN/GRP receptor antagonists such as (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin (6-14) (RC-3095) as poten- tial anticancer drugs [2,13]. ∗ Corresponding author. Tel.: +55-51-3316-3183; fax: +55-51-3316-3121. E-mail address: rroesler@terra.com.br (R. Roesler). In addition to regulating normal CNS function, BN-like peptides might be involved in neuropsychiatric disorders such as schizophrenia and autism. Schizophrenic patients show decreased BN levels [4,11], and the GRP receptor gene (GRPR) has been proposed as a candidate gene for autism [6]. In addition, administration of BN can induce stereotyped behaviors in rodents [7,9,10,12,14]. Stereotyped behaviors are features of psychiatric disorders such as schizophrenia and obsessive–compulsive disorder. Stereotyped behaviors induced by systemic administration of the dopamine re- ceptor agonist apomorphine or the N-methyl-d-aspartate glutamate receptor channel blocker dizocilpine (MK-801) in rodents have been considered animal models of psy- chosis that are useful for the preclinical screening of drugs with potential antipsychotic activity [1,5,15,17]. In the present study, we examined the effects of systemic 0196-9781/$ – see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.peptides.2004.01.003