Behavioural Brain Research 263 (2014) 60–69 Contents lists available at ScienceDirect Behavioural Brain Research jou rn al hom epage: www.elsevier.com/locate/bbr Research report Long-term behavioral effects of neonatal blockade of gastrin-releasing peptide receptors in rats: Similarities to autism spectrum disorders Z. Merali a,b,c,e,∗ , J. Presti-Torres e,f , J.C. MacKay a,e , J. Johnstone a,e , L. Du e , A. St-Jean a , D. Levesque a , P. Kent a,e , G. Schwartsmann g,h,i , R. Roesler h,i,j , N. Schroder f,i , H. Anisman d,e a School of Psychology, University of Ottawa, Ottawa, ON K1N 6N5, Canada b Department of Psychiatry, University of Ottawa, Ottawa, ON K1N 6N5, Canada c Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada d Institute of Neuroscience, Carleton University, Ottawa, ON, K1S 5B6, Canada e University of Ottawa, Institute of Mental Health Research, Ottawa, ON, K1Z 7K4, Canada f Neurobiology and Developmental Biology Laboratory, Pontifical Catholic University, Porto Alegre, 90619-900, Brazil g Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil h Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil i National Institute for Translational Medicine (INCT-TM), 90035-003, Porto Alegre, RS, Brazil j Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170, Porto Alegre, RS, Brazil h i g h l i g h t s • Neonatal blockade of GRP receptors caused long term behavioral deficits. • Rats showed reduced sociability, restrictive interests, motor stereotypies and increased fear. • These behavioral abnormalities are similar to autism. • Neonatal GRP receptor blockade may provide insight into autism-relevant phenotypes. a r t i c l e i n f o Article history: Received 20 November 2013 Received in revised form 10 January 2014 Accepted 13 January 2014 Available online 23 January 2014 Keywords: Gastrin-releasing peptide receptor RC-3095 Social interaction Restrictive behavior Learned fear Autism spectrum disorder a b s t r a c t Gastrin releasing peptide, the mammalian counterpart of the amphibian peptide, bombesin, has been increasingly implicated in regulating normal brain function as well as in the pathogenesis of psychi- atric and/or neurodevelopmental disorders. We have previously shown that the neonatal blockade of the gastrin-releasing peptide receptor (GRPr) in rats produces long-lasting consequences during central ner- vous system development that are commonly observed in neurodevelopmental disorders such as autism spectrum disorders. The present investigation assessed in further detail, long-term behavioral effects of neonatal GRPr blockade. During postnatal days 1–10, male Wistar rat pups (n = 5–10/litter) were injected (subcutaneously) with the GRPr antagonist, RC-3095 (1 mg/kg), or a vehicle (control), twice daily. Follow- ing the drug treatment regimen, several behaviors were assessed (starting on postnatal day 14) including specific social behaviors (namely, group huddling characteristics, social interaction, and social approach), restrictive/repetitive and stereotyped behaviors (y-maze, repetitive novel object contact task, observa- tion for stereotypies) and anxiety/fear-related responses (open field, elevated plus maze and contextual fear conditioning). Rats treated neonatally with RC-3095 showed reduced sociability, restrictive inter- ests, motor stereotypies and enhanced learned fear response compared to the controls (vehicle-treated rats). These behavioral abnormalities are consistent with those observed in autism spectrum disorders and provide further evidence that neonatal blockade of GRPr could potentially serve as a useful model to gain a better understanding of the underlying neurodevelopmental disruptions contributing to the expression of autism-relevant phenotypes. © 2014 Elsevier B.V. All rights reserved. ∗ Corresponding author at: University of Ottawa Institute of Mental Health Research 1145 Carling Avenue Rm 5432, Research Tower Ottawa, ON, K1Z 7K4, Canada. Tel.: +1 613 722 6521x6551; fax: +1 613 792 3935. E-mail address: merali@uottawa.ca (Z. Merali). 0166-4328/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.bbr.2014.01.008