title: Rescue of social behavior impairment by clozapine and alterations in the expression of neuronal receptors in a rat model of neurodevelopmental impairment induced by GRPR blockade.
abstract: We have previously shown that pharmacological blockade of the gastrin-releasing peptide receptor (GRPR) during the neonatal period in rats produces behavioral features of developmental neuropsychiatric disorders. Here, we show that social interaction deficits in this model are reversed by the atypical antipsychotic clozapine given in the adulthood. In addition, we analyzed the mRNA expression of three neuronal receptors potentially involved in the etiology of disorders of the autism spectrum. Rats were injected with the GRPR antagonist RC-3095 or saline (SAL) from postnatal days 1-10, and tested for social behavior and recognition memory in the adulthood. One hour prior to the behavioral testing, rats were given a systemic injection of clozapine or saline. The mRNA expression of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor, the epidermal growth factor receptor (EGFR), and GRPR was measured in the hippocampus and cortex of a separate set of rats given RC-3095 or SAL neonatally. Rats given neonatal RC-3095 showed decreased social interaction and impaired object recognition memory. Clozapine rescued the social interaction impairment. Neonatal treatment with RC-3095 also resulted in dose-dependent decreases in the expression of GRPR, NR1, and EGFR in the cortex, whereas all three receptor mRNAs were increased in the hippocampus in rats treated with the lower dose of RC-3095. The results contribute to further validate the novel rat model of neurodevelopmental disorders induced by GRPR blockade, and shows alterations in the expression of neuronal receptors in this model.
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, Av. Ipiranga, 6681 Prédio 12D, Sala 340, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Presti-Torres
authors.forename: Vanessa Athaíde
authors.initials: VA
authors.lastname: Garcia
authors.forename: Arethuza
authors.initials: A
authors.lastname: Dornelles
authors.forename: Luís Henrique
authors.initials: LH
authors.lastname: Halmenschlager
authors.forename: Luisa Azambuja
authors.initials: LA
authors.lastname: Alcalde
authors.forename: Gustavo
authors.initials: G
authors.lastname: Vedana
authors.forename: Eduardo Pacheco
authors.initials: EP
authors.lastname: Rico
authors.forename: Maurício Reis
authors.initials: MR
authors.lastname: Bogo
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
authors.forename: Nadja
authors.initials: N
authors.lastname: Schröder
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D012919:Social Behavior
chemical_list: D014150:Antipsychotic Agents; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D003024:Clozapine; D001839:Bombesin