TABLE 8.
Studies investigating the effects of folate on depressive-like behavior.
| Treatment | Species or strain | Model | Behavioral outcomes | Molecular mechanisms | Reference |
|---|---|---|---|---|---|
| Folic acid (75 mg/kg) | Male Sprague-Dawley rats | CUMS | Improvement of depression-like behaviors as assessed in FST, TST and OFT | ↑5-HT, BDNF and GluR1 expression; changes in synaptic organisation in the brain | [227] |
| Folic acid (p.o. and i.c.v.) + PCPA (100 mg/kg) or fluoxetine (10 mg/kg, p.o.) or WAY100635 (0.1 mg/kg, s.c.) or ketanserin (5 mg/kg) or yohimbine (1 mg/kg, i.p.) | Male and female Swiss mice | - | ↓immobility time in the FST; no effect on locomotor activity; PCPA blocked the decrease in immobility time elicited by folic acid; co-administration of a subeffective fluoxetine produced a synergistic effect with a subeffective dose of folic acid; WAY100635 significantly blocked the decrease in immobility time in the FST elicited by full dose of folic acid; WAY100635 produced a synergistic effect with a subeffective dose of folic acid; ketanserin blocked the decrease in immobility time in the FST elicited by folic acid; yohimbine was also able to prevent the anti-immobility effect the folic acid | - | [226] |
| folic acid (10 nmol/site, i.c.v.) + naloxone (1 mg/kg, i.p.) or naltrindole (3 mg/kg, i.p.) or naloxonazine (10 mg/kg, i.p.) or naloxone methiodide (1 mg/kg, s.c.) | Male and female Swiss mice | - | Naloxone, naltrindole, naloxonazine, but not naloxone methiodide, prevented the antidepressant-like effect of folic acid in the FST; folic acid + morphine had a synergistic anti-depressant effect in the FST (but no effect on locomotion); naloxone reversed the anti-depressant properties of folic acid + MK-801 | - | [232] |
| Folate-depleted vs folate-supplemented diets | Adult male and female Wistar Kyoto rats | ELS (maternal separation) | dietary methyl donor supplementation induced ↑ exploratory behavior in the OFT, exhibit ↑social behavior and ↓ immobile time in the FST | ↑DNA methylation in the hippocampus of mice exposed to maternal separation; ↑brain methionine levels in rats supplemented with methyl donors | [234] |
| Methyl donor supplementation (choline, betaine, folate, vitamin B12) for 18 weeks | Wistar rats | ELS (maternal separation) | ↓depressive behavior in the Porsolt FST | normalisation of total and HDL-cholesterol; ↑total DNA methylation and ↑hippocampal (not hypothalamic) expression of the insulin receptor | [213] |
| Folic acid (5 or 10 nmol/i.c.v.; 25, 50 or 75 mg/kg p.o.), or fluoxetine (20 or 25 mg/kg) or 17-β estradiol (10 or 20 μg/rat); combination of folic acid (2.5 nmol/i.c.v.; or 25.0 mg/kg, p.o.) + fluoxetine (15.0 mg/kg); combination of folic acid (2.5 nmol/i.c.v.; or 25.0 mg/kg, p.o.) + 17-β estradiol (5 μg/rat) | Female Wistar rats | ovariectomized | ↓ immobility in the FST; antidepressant effects were not achieved if ketanserin was admnistered. | - | [228] |
5-HT: 5-Hydroxytryptamine; BDNF: Brain-Derived Neurotrophic Factor; CUMS: Chronic Unpredictable Mild Stress; ELS: Early-Life Stres; FST: Forced-Swim Test; GluR1: Glutamate Receptor 1; HDL: High-Density Lipoprotein; MK-801: Non-Competitive NMDA Receptor Antagonist; OFT: Open Field Test; PCPA: Para-Chlorophenylalanine; TST: Tail Suspension Test; WAY100635: 5-HT1A Receptor Antagonist And Full D4 Receptor Agonist.