IMR Press / JIN / Volume 23 / Issue 3 / DOI: 10.31083/j.jin2303051
Open Access Original Research
Involvement of the GABAA Receptor in the Antidepressant-Like Effects Produced by Low and High Doses of the Flavonoid Chrysin in the Rat: A Longitudinal Study
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1 Researchers Program by Mexico, CONAHCYT –Neuroethology Institute, Universidad Veracruzana, 91190 Xalapa, Veracruz, Mexico
2 Neuropharmacology Laboratory, Neuroethology Institute, Universidad Veracruzana, 91190 Xalapa, Veracruz, Mexico
3 Faculty of Pharmaceutical and Biological Chemistry, Universidad Veracruzana, 91000 Xalapa, Veracruz, Mexico
4 PhD Program in Neuroethology, Neuroethology Institute, Universidad Veracruzana, 91190 Xalapa, Veracruz, Mexico
5 Faculty of Pharmaceutical and Biological Chemistry, Inter-American University Center, 94470 Cordoba, Veracruz, Mexico
*Correspondence: (Gabriel Guillén-Ruiz); (Blandina Bernal-Morales)
These authors contributed equally.
J. Integr. Neurosci. 2024, 23(3), 51;
Submitted: 1 September 2023 | Revised: 7 November 2023 | Accepted: 8 December 2023 | Published: 4 March 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

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 (GABAA) 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 GABAA 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 GABAA 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.

GABAA receptor
log-term effect
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Fig. 1.
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