Antidepressant-like effect of leptin in streptozotocin-induced diabetic mice

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2007, Vol.86 (1), p.27-31
• Main Authors: Hirano, Shoko, Miyata, Shigeo, Kamei, Junzo
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Antidepressive Agents; Biological and medical sciences; Blood Glucose - metabolism; Body Weight - physiology; Depression; Depressive-like behavior; Diabetes; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - psychology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Ergolines - pharmacology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Hindlimb Suspension; Insulin - blood; Leptin; Leptin - blood; Leptin - pharmacology; Male; Medical sciences; Mice; Mice, Inbred ICR; Mood disorders; Motor Activity - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Piperazines - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Pyridines - pharmacology; Receptor, Serotonin, 5-HT1A - drug effects; Receptors, Leptin; Receptors, Serotonin, 5-HT2 - drug effects; Serotonin; Serotonin Antagonists - pharmacology; Tail suspension test
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2006.12.003

We previously reported that streptozotocin (STZ)-induced diabetic mice showed the depressive-like behavior in the tail suspension test. It has also been reported that leptin-deficient obese mice demonstrate the depressive-like behavior. Since STZ-induced diabetes causes a marked decrease in plasma leptin levels, it is possible that decrease in leptin levels and the depressive-like behavior may somehow be related. Therefore, we examined the effect of leptin on the depressive-like behavior of STZ-induced diabetic mice in the tail suspension test. The prolonged duration of immobility in diabetic mice was dose-dependently and significantly suppressed by single treatment with leptin (0.1–1 mg/kg, i.p.) without affecting on the locomotor activity. Leptin did not affect either the duration of immobility or the locomotor activity in non-diabetic mice. The anti-immobility effect of leptin (1 mg/kg, i.p.) in diabetic mice was significantly antagonized by the selective serotonin 2 (5-HT 2) receptor antagonist LY53,857 (0.03 mg/kg, s.c.), but not by the selective 5-HT 1A receptor antagonist WAY-100635 (0.03 mg/kg, s.c.). Antagonists administered alone did not affect either the duration of immobility or the locomotor activity in diabetic mice. In conclusion, we suggest that leptin exerts the antidepressant-like effect in diabetic mice mediated by, at least in part, 5-HT 2 receptors.