title: Glucagon-like peptide-2 but not imipramine exhibits antidepressant-like effects in ACTH-treated mice.
abstract: We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) against refractory depression in adrenocorticotropic hormone (ACTH)-treated mice as a model of tricyclic antidepressant (TCA)-resistant depression. Chronic ACTH treatment (0.45 mg/kg, s.c., 14 days) weakened the antidepressant-like effects of imipramine (20 mg/kg, i.p., 6 days) in the forced-swim test (FST). Conversely, GLP-2 (3 μg/mice, i.c.v., 6 days) induced antidepressant-like effects in the ACTH-treated mice in the FST. ACTH-treatment increased basal serum corticosterone levels, with an additional increase induced by the FST. Imipramine or GLP-2 had no effect on the basal corticosterone level, but GLP-2 attenuated the additional increase caused by the FST. Moreover, GLP-2 increased 5-HT levels, but not 5-HIAA. These results suggest that GLP-2 induced antidepressant-like effects under imipramine-resistant conditions through increase in 5-HT levels.
authors: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors: Takashi
authors: T
authors: Iwai
authors: Tomoko
authors: T
authors: Ohnuki
authors: Sachie
authors: S
authors: Sasaki-Hamada
authors: Akiyoshi
authors: A
authors: Saitoh
authors: Azusa
authors: A
authors: Sugiyama
authors: Jun-Ichiro
authors: J
authors: Oka
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D061218:Depressive Disorder, Treatment-Resistant / Q000139:chemically induced / Q000188:drug therapy; D004195:Disease Models, Animal; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage / Q000502:physiology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D053767:Glucagon-Like Peptide 2; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000324:Adrenocorticotropic Hormone; D007099:Imipramine