title: Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis.
abstract: Recent studies indicate a high comorbidity between type-2 diabetes mellitus (T2DM) and neurological disorders. Many are associated with abnormalities in dopamine neurotransmission such as schizophrenia. Because most of the antipsychotic drugs aggravate pre-existing insulin resistance in type-2 diabetics, there is a need to search for alternative antipsychotics. Glucagon like peptide-1 (GLP-1) is a gut hormone primarily involved in glucose homeostasis. GLP-1 agonist (liraglutide) and dipeptidyl peptidase-IV (DPP-IV) inhibitor (sitagliptin) are the US-FDA approved medications for the management of T2DM. However, little is known about their role in dopamine mediated neurological disorders like schizophrenia. To address this, we used apomorphine-induced cage climbing behavior as a murine model for psychosis and examined for potential antipsychotic-like effect of liraglutide and sitagliptin. While acute liraglutide treatment (50 μg/kg; i.p.) significantly attenuated apomorphine (3 mg/kg, s.c.) induced cage climbing, sitagliptin (50mg/kg; i.p.) failed to elicit such effect. This is the first preclinical evidence for antipsychotic-like effect of GLP-1 receptor agonist. These results open an opportunity to explore GLP-1 analogs for their potential to modulate spectrum of dopamine-mediated neurological disorders.
authors.affiliation: Department of Pharmacology, S.T.E.S.s Smt. Kashibai Navale College of Pharmacy, Kondhwa (Bk), Pune, MS 411048, India.
authors.forename: Tejashree S
authors.initials: TS
authors.lastname: Dixit
authors.forename: Ajaykumar N
authors.initials: AN
authors.lastname: Sharma
authors.forename: James B
authors.initials: JB
authors.lastname: Lucot
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Elased
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001058:Apomorphine / Q000633:toxicity; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000633:toxicity; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069450:Liraglutide; D008297:Male; D051379:Mice; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000209:etiology; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D018709:Statistics, Nonparametric; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D011719:Pyrazines; D014230:Triazoles; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D001058:Apomorphine; D000068900:Sitagliptin Phosphate