title: Neurobehavioral effects of liraglutide and sitagliptin in experimental models.
abstract: Glucagon-like peptide (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors are two currently approved therapies for type 2 diabetes mellitus (T2DM). Present study evaluated the effect of liraglutide (a long-acting GLP-1 agonist) and sitagliptin (a DPP-4 inhibitor) on nociception, anxiety, depression-like behavior and cognition in rats or mice. Nociception was assessed using tail-flick test; anxiety-behavior in open-field test and elevated plus maze (EPM) test while depression-like behavior was evaluated in forced swim test (FST) and tail-suspension test (TST). Cognition was assessed in EPM and Morris water maze (MWM) following memory deficit induced by pentylenetetrazole (PTZ) or scopolamine. In tail-flick test sitagliptin (6 mg/kg) produced transient nociceptive effect. Liraglutide (200 µg/kg) reduced peripheral square crossings by rats in open field test as well as reduced closed arm entries in the EPM, indicating a decline in exploratory behavior. In FST and TST models for depression, the duration of immobility with sitagliptin (6 mg/kg) was reduced significantly in comparison to control group suggesting its antidepressant effect. Liraglutide did not show any antidepressant action. In EPM test for cognition, liraglutide and sitagliptin ameliorated the increase in transfer latency caused by PTZ in a dose-dependent manner. In MWM liraglutide and sitagliptin prevented the scopolamine-induced increase of the escape latency. This study shows that sitagliptin has mild antinociceptive effect and anti-depressant effect in the animal models of depression while liraglutide did not have such an effect. Liraglutide showed anxiogenic effects in the animal models. Both liraglutide and sitagliptin produced cognitive improvement in the animal models.
authors: Department of Pharmacology, Lady Hardinge Medical College & Smt. S.K. Hospital, New Delhi 110001, India.
authors: Mayur
authors: M
authors: Kamble
authors: Department of Pharmacology, University College of Medical Sciences & GTB Hospital, New Delhi 110095, India.
authors: Rachna
authors: R
authors: Gupta
authors: Department of Pharmacology, Lady Hardinge Medical College & Smt. S.K. Hospital, New Delhi 110001, India.
authors: Harmeet S
authors: HS
authors: Rehan
authors: Department of Pharmacology, Lady Hardinge Medical College & Smt. S.K. Hospital, New Delhi 110001, India. Electronic address: lkg71@rediffmail.com.
authors: Lalit K
authors: LK
authors: Gupta
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003071:Cognition / Q000187:drug effects; D003863:Depression / Q000188:drug therapy; D004195:Disease Models, Animal; D000069450:Liraglutide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D059225:Nociception / Q000187:drug effects; D051381:Rats; D000068900:Sitagliptin Phosphate / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000069450:Liraglutide; D000068900:Sitagliptin Phosphate
keywords: Anxiety; Cognition; Depression; GLP-1; Liraglutide; Sitagliptin