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Synergistic antidepressant-like effect of capsaicin and citalopram reduces the side effects of citalopram on anxiety and working memory in rats

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Abstract

Rationale

We have previously shown that in rats, capsaicin (Cap) has antidepressant-like properties when assessed using the forced swimming test (FST) and that a sub-threshold dose of amitriptyline potentiates the effects of Cap. However, synergistic antidepressant-like effects of the joint administration of Cap and the selective serotonin reuptake inhibitor citalopram (Cit) have not been reported.

Objectives

To assess whether combined administration of Cap and Cit has synergistic effects in the FST and to determine whether this combination prevents the side effects of Cit.

Methods

Cap, Cit, and the co-administration of both substances were evaluated in a modified version of the FST (30-cm water depth) conducted in rats, as well as in the open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM).

Results

In line with previous studies, independent administration of Cap and Cit displayed antidepressant-like properties in the FST, while the combined injection had synergistic effects. In the OFT, neither treatment caused significant increments in locomotion. In the EPM, the time spent in the closed arms was lower in groups administered either only Cap or a combination of Cap and Cit than in groups treated with Cit alone. In the MWM, both Cap and the joint treatment (Cap and Cit) improved the working memory of rats in comparison with animals treated only with Cit.

Conclusion

Combined administration of Cap and Cit produces a synergistic antidepressant-like effect in the FST and reduces the detrimental effects of Cit on anxiety and working memory.

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Abbreviations

Cap:

Capsaicin

Cit:

Citalopram

ED50 :

Dose required to achieve 50% of the maximal effect

EPM:

Elevated plus maze

FST:

Forced swimming test

NZ:

Neutral zone

OFT:

Open field test

MWM:

Morris water maze

SSRIs:

Selective serotonin reuptake inhibitors

TRPV1:

Transient receptor potential cation channel subfamily V member 1

Veh:

Vehicle

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Acknowledgments

The authors wish to thank M.Sc. Fernando J. Álvarez-Cervera (Universidad Autónoma de Yucatán) for editorial assistance.

Funding

CONACYT CB-254887 to JA, and CONACYT 256878 to JLGA.

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Authors and Affiliations

  1. Centro Universitario de Investigaciones Biomédicas “CUIB”, Universidad de Colima, Av. 25 de Julio # 965, Col. Villas de San Sebastián, Colima, Colima, Mexico

    Irving S. Aguilar-Martinez, Miriam E. Reyes-Mendez, J. Manuel Herrera-Zamora, Fernando Osuna-Lopez, Adolfo Virgen-Ortiz, Eloy G. Moreno-Galindo & Javier Alamilla

  2. Facultad de Ciencias Quimicas, Universidad de Colima, Colima, Colima, Mexico

    Nestor Mendoza-Munoz

  3. Departamento de Neurociencias, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico

    Jose L. Gongora-Alfaro

  4. Consejo Nacional de Ciencia y Tecnología (CONACYT), Universidad de Colima, Colima, Colima, Mexico

    Javier Alamilla

Authors
  1. Irving S. Aguilar-Martinez
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  2. Miriam E. Reyes-Mendez
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  3. J. Manuel Herrera-Zamora
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  4. Fernando Osuna-Lopez
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  5. Adolfo Virgen-Ortiz
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  6. Nestor Mendoza-Munoz
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  7. Jose L. Gongora-Alfaro
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  8. Eloy G. Moreno-Galindo
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  9. Javier Alamilla
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Corresponding author

Correspondence to Javier Alamilla.

Ethics declarations

All experimental procedures were revised and approved by the Institutional Bioethics Committee of the University Center for Biomedical Research of the University of Colima, in Mexico, and were performed in accordance with the Guide for the Care and Use of Laboratory Animals of the US National Institutes of Health (NIH Publication No. 85-23, revised 1996).

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Aguilar-Martinez, I.S., Reyes-Mendez, M.E., Herrera-Zamora, J.M. et al. Synergistic antidepressant-like effect of capsaicin and citalopram reduces the side effects of citalopram on anxiety and working memory in rats. Psychopharmacology 237, 2173–2185 (2020). https://doi.org/10.1007/s00213-020-05528-6

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