Table 2.
Overview of Leptin’s effect on depression in experimental models
| Model | Behavioral assessment | Main findings | Mechanism | Refs. |
|---|---|---|---|---|
| CUS rats CSDS rats | FST | CUS rats and CSDS rats displayed low leptin levels in plasma. Systemic leptin administration reversed the CUS-induced hedonic-like deficit and improved behavioral despair dose-dependently | 64 | |
| CSDS mice | EPM, FST | Stressed mice have lower serum leptin levels than controls. CSDS mice displayed central leptin resistance; administration of a melanocortin agonist worsens stress-induced behavioral deficits, while mice lacking the melanocortin 4-receptor display attenuated symptoms | β3-adrenergic receptors | 65 |
| Lep (ob/ob) mice LepTg mice DIO mice | FST, SPT | Excess leptin reversed depression-like behaviors; leptin failed to induce an antidepressant action or alter c-Fos expression in the hippocampus of DIO mice, but significantly increased hippocampal BDNF concentrations in CD mice | TrkB/BDNF signaling pathway in hippocampus | 67 |
| LeprDAT-Cre mice (LepRb was selectively deleted in dopamine neurons.) | SPT, FST, TST | LeprDAT-Cre mice displayed an anxiogenic-like phenotype, while depression-like behaviors were not affected; microinjection of the D1 antagonist SCH23390 into the CeA attenuated the anxiogenic phenotype | DA signalings in midbrain | 70 |
| CUS rats | OFT, SPT, FST | Leptin administration reversed the CUS-induced reduction of hippocampal neurogenesis and depression-like behaviors; leptin increased β-catenin and reversed the inhibitory effects of dexamethasone on β-catenin | GSK-3β/β-catenin signaling-dependent neurogenesis | 66 |
| LepRb cKO mice (LepRb was ablated in glutamatergic neurons of forebrain) | FST, TST, RT, SPT, LHT, Hot-plate test, EPM, OFT, LDT | Lepr cKO mice displayed depression-like behavioral deficits loss of Lepr in forebrain glutamatergic neurons facilitated NMDA-induced hippocampal LTD | NMDA-mediated LTD | 73 |
| LepRb (db/db) mice | SPT, FST, TST, LA | LepRb (db/db) displayed resistance to treatment with either fluoxetine or desipramine; fluoxetine failed to stimulate phosphorylation of Akt(Thr308) and GSK-3β(Ser9) in the hippocampus and PFC of db/db mice | Akt/GSK signaling | 68 |
| LepRb (db/db) mice | SPT, FST, TST, OFT | LepRb (db/db) mice displayed depression-like behaviors; STAT3 activity and phosphorylation at Tyr 705 were decreased by LepRb KO, which did not involve iIKKb/NFjB signaling | STAT3/SOCS3 signaling | 69 |
CSDS chronic social defeat stress, CUS chronic unpredictable stress, LA locomotor activity, TST tail suspension test, FST forced swim test, SPT saccharin preference test, LHT learned helplessness test, EPM elevated plus-maze, OFT open-field test, LDT light dark test, RT rotarod test, LepTg mice (transgenic skinny mice overexpressing leptin in the liver), LTD long-term depression, DIO diet-induced obesity