Antidepressant-like effect of leptin in streptozotocin-induced diabetic mice.
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 serotonin2 (5-HT2) receptor antagonist LY53,857 (0.03 mg/kg, s.c.), but not by the selective 5-HT1A 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-HT2 receptors.
Hirano
Shoko
S
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan.
Miyata
Shigeo
S
Kamei
Junzo
J
D000818:Animals; D000928:Antidepressive Agents; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000523:psychology*; D004873:Ergolines / Q000494:pharmacology; D019417:Hindlimb Suspension; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D054411:Receptors, Leptin; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology
D000928:Antidepressive Agents; D001786:Blood Glucose; D004873:Ergolines; D007328:Insulin; D020738:Leptin; D010879:Piperazines; D011725:Pyridines; D054411:Receptors, Leptin; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; C515447:leptin receptor, mouse; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C032663:LY 53857