title: A gastrin-releasing peptide receptor antagonist blocks D-amphetamine-induced hyperlocomotion and increases hippocampal NGF and BDNF levels in rats.
abstract: The gastrin-releasing peptide receptor (GRPR) has emerged as a novel molecular target in neurological and psychiatric disorders, and previous animal studies suggest that GRPR antagonists might display cognitive-enhancing and antipsychotic properties. Hyperlocomotion produced by administration of D-amphetamine (D-AMPH) to rats has been put forward as a model of the manic phase of bipolar disorder (BD). In the present study, we examined the effects of a single systemic administration of the GRPR antagonist [D-Tpi(6), Leu(13) psi(CH(2)NH)-Leu(14)] bombesin (6-14) (RC-3095) on hyperlocomotion induced by a single systemic injection of D-AMPH in male rats. We also evaluated the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus of rats treated with D-AMPH and RC-3095. Administration of RC-3095 at any of the doses used blocked D-AMPH-induced hyperlocomotion. Specific doses of RC-3095 increased the levels of NGF and BDNF in the dorsal hippocampus. Administration of D-AMPH did not affect NGF or BDNF levels by itself, but blocked the RC-3095 effects. The results suggest that GRPR antagonists might display anti-manic activity.
authors.affiliation: Laboratory of Experimental Psychiatry and Bipolar Disorders Program, Academic Hospital Research Center, Department of Biochemistry, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Márcia
authors.initials: M
authors.lastname: Kauer-Sant'Anna
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Andreazza
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.forename: Márcio Rodrigo
authors.initials: MR
authors.lastname: Martins
authors.forename: Luciana M
authors.initials: LM
authors.lastname: Barbosa
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism; D001839:Bombesin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D020932:Nerve Growth Factor / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D020932:Nerve Growth Factor; D001839:Bombesin; D003913:Dextroamphetamine