Background: The flavonoid chrysin produces rapid and long-lasting
anxiolytic- and antidepressant-like effects in rats. However, it is not known
whether low and high doses of chrysin produce differential anti-immobility
effects through the Gamma-Aminobutyric Acid sub-type A (GABA) receptor. The
goal of this work was therefore to compare low and high doses of chrysin for
their effects on depression-like behavior in a longitudinal study. Moreover,
chrysin was compared with the serotonergic fluoxetine and Gamma-Aminobutyric Acid
(GABA)ergic allopregnanolone, and its involvement with the GABA receptor
after chronic treatment was also investigated. Methods: Male Wistar rats
were assigned to five groups (n = 8 each): vehicle, 1 mg/kg chrysin, 5 mg/kg
chrysin, 1 mg/kg fluoxetine, and 1 mg/kg allopregnanolone. In the first
experiment, treatments were injected daily and the effects on locomotor activity
and the forced swim test were evaluated at 0, 1, 14, and 28 days of treatment,
and 48 h after the final treatment. In the second experiment, similar groups were
treated for 28 days with injection of 1 mg/kg picrotoxin to investigate the role
of the GABA receptor. Depending on the experimental design, one- and
two-way analysis of variance (ANOVA) tests were used for statistical analysis,
with p 0.05 set as the criteria for significance. Results:
In both experiments, the treatments did not alter locomotor activity. However,
low and high doses of chrysin, allopregnanolone, and fluoxetine gradually
produced antidepressant-like effects in the forced swim test, and maintained this
effect for 48 h post-treatment, except with low dose chrysin. Picrotoxin blocked
the antidepressant-like effects produced by low dose chrysin, but did not affect
those produced by high dose chrysin, allopregnanolone, or fluoxetine.
Conclusions: The differential antidepressant-like effects caused by low
and high doses of chrysin are time-dependent. Low dose chrysin produces a rapid
antidepressant-like effect, whereas high dose chrysin produces a delayed but
sustained the effect, even 48 h after withdrawal. The effect with high dose
chrysin was similar to that observed with allopregnanolone and fluoxetine. The
mechanism for the antidepressant-like effect of low chrysin appears to be
GABAergic, whereas the effect of high dose chrysin may involve other
neurotransmission and neuromodulation systems related to the serotonergic system.