A gastrin-releasing peptide receptor antagonist blocks d-amphetamine-induced hyperlocomotion and increases hippocampal NGF and BDNF levels in rats

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-Tpi6, Leu13 psi(CH2NH)-Leu14] 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.