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

Pharmacol Biochem Behav. 2007 Jan;86(1):27-31. doi: 10.1016/j.pbb.2006.12.003. Epub 2006 Dec 20.


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.

MeSH terms

  • Animals
  • Antidepressive Agents*
  • Blood Glucose / metabolism
  • Body Weight / physiology
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / psychology*
  • Ergolines / pharmacology
  • Hindlimb Suspension
  • Insulin / blood
  • Leptin / blood
  • Leptin / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptors, Leptin
  • Receptors, Serotonin, 5-HT2 / drug effects
  • Serotonin Antagonists / pharmacology


  • Antidepressive Agents
  • Blood Glucose
  • Ergolines
  • Insulin
  • Leptin
  • Piperazines
  • Pyridines
  • Receptors, Leptin
  • Receptors, Serotonin, 5-HT2
  • Serotonin Antagonists
  • leptin receptor, mouse
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • LY 53857