TABLE 5.
Studies investigating the effects of lactate on depressive-like behavior.
| Treatment | Species or strain | Model | Behavioral outcomes | Molecular mechanisms | Reference |
|---|---|---|---|---|---|
| L-lactate (1 g/kg, ip, either acute or chronic (daily for 3 weeks)) | C57Bl/6 mice (8-10 weeks) | corticosterone model of depression (for chronic experiment only) | Chronic treatment ↓ immobility in the FST to a similar extent as desipramine; chronic treatment abolished the increased immobility induced by corticosterone treatment in the FST and TST, reversed the corticosterone-induced decrease in saccharin consumption and decreased the immobility time in the open-space forced swim model of depression to a similar extent as desipramine | Acute effects: ↓ GSK3α and GSK3β in the hippocampus; ↓ phospho-CREB levels in the hippocampus; ↑hippocampal Arc, COX-2 and NOS1 mRNA expression; ↓COX-2 mRNA in the hippocampus. Chronic effects: ↑mRNA and protein levels encoding the regulator of serotonin receptors p11, the astrocytic marker S100β1 and the transcription factor Hes534 in the hippocampus of animals subjected to the open-space FST compared with vehicle-treated animals; ↓expression of PDE4D and NOS1 both at the mRNA and protein levels in the hippocampus of animals subjected to the open-space FST compared with vehicle-treated animals. | [174] |
| Lactate (during experimental stress period) or lactate + CI-994 (after experimental stress period) | male C57Bl/6 mice (8-10 weeks) | CSDS | Before the establihsment of depression: Reverses social avoidance and anxiety. After the establihsment of depression: reduced depression-like behavior | Before the establihsment of depression: Restores hippocampal class I HDAC2/3 levels and activity. After the establihsment of depression: hippocampal class II HDAC5 deactivation | [173] |
Arc: Activity-Regulated Cytoskeleton-Associated Protein; COX-2: Cyclooxygenase 2; CREB: Camp Response Element-Binding Protein; CSDS: Chronic Social Defeat Stress; FST: Forced-Swim Test; GSK3α/β: Glycogen synthase kinase 3 alpha/beta; HDAC2/3/5: Histone Deacetylase 2/3/5; NOS1: Nitric Oxide Synthase 1; PDE4D: Camp-Specific 3′,5′-Cyclic Phosphodiesterase 4D; TST: Tail Suspention Test.