Evidence for the involvement of the opioid system in the antidepressant-like effect of folic acid in the mouse forced swimming test.
Brocardo PS, Budni J, Lobato KR, Santos AR, Rodrigues AL.
Departamento de Bioquímica,
Centro de Ciências Biológicas,
Universidade Federal de Santa Catarina,
Campus Universitário -Trindade,
88040-900 Florianópolis, SC, Brazil.
Behav Brain Res. 2009 Jun 8;200(1):122-7.


The opioid system has been implicated in major depression and in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of the water-soluble B-vitamin folic acid in the forced swimming test (FST). The effect of folic acid (10nmol/site, i.c.v.) was prevented by the pretreatment of mice with naloxone (1mg/kg, i.p., a nonselective opioid receptor antagonist), naltrindole (3mg/kg, i.p., a selective delta-opioid receptor antagonist), naloxonazine (10mg/kg, i.p., a selective mu(1)-opioid receptor antagonist, 24h before), but not with naloxone methiodide (1mg/kg, s.c., a peripherally acting opioid receptor antagonist). In addition, a sub-effective dose of folic acid (1nmol/site, i.c.v.) produced a synergistic antidepressant-like effect in the FST with a sub-effective dose of morphine (1mg/kg, s.c.). A further approach was designed to investigate the possible relationship between the opioid system and NMDA receptors in the mechanism of action of folic acid in the FST. Pretreatment of the animals with naloxone (1mg/kg, i.p.) prevented the synergistic antidepressant-like effect of folic acid (1nmol/site, i.c.v.) and MK-801 (0.001mg/kg, i.p., a non-competitive NMDA receptor antagonist). Together the results firstly indicate that the anti-immobility effect of folic acid in the FST is mediated by an interaction with the opioid system (mu(1) and delta), likely dependent on the inhibition of NMDA receptors elicited by folic acid.
TCA mechanisms
Atypical depression
Retarded depression
Hippocampal remdelling
Selectivity or multiplicity?
Noradrenaline and dopamine
The hippocampus in depression
ECT, melancholia and hippocampal neogenesis
Folic acid deficiency and neuropsychiatric disease
Depression, antidepressants and the hippocampus
Desipramine, antidepressants and the opioid system
Desipramine and the postsynaptic alpha-2 adrenergic receptors

and further reading

Future Opioids
BLTC Research
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family