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Acute antidepressant effect of ayahuasca in juvenile non-human primate model of depression

Flávia Santos da Silva, Erick Allan dos Santos Silva, Geovan Menezes de Sousa Junior, Joao Paulo Maia-de-Oliveira, Vanessa de Paula Soares Rachetti, Draulio Barros de Araujo, Maria Bernardete Cordeiro de Sousa, Bruno Lobão Soares, Nicole Leite Galvão-Coelho
doi: https://doi.org/10.1101/254268
Flávia Santos da Silva
1Postgraduate Program in Psychobiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
2Laboratory of Hormone Measurement, Department of Physiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
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Erick Allan dos Santos Silva
2Laboratory of Hormone Measurement, Department of Physiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
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Geovan Menezes de Sousa Junior
2Laboratory of Hormone Measurement, Department of Physiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
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Joao Paulo Maia-de-Oliveira
3Department of Clinical Medicine, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
4National Institute of Science and Technology in Translational Medicine Natal, RN, Brazil;
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Vanessa de Paula Soares Rachetti
5Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
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Draulio Barros de Araujo
6Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
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Maria Bernardete Cordeiro de Sousa
1Postgraduate Program in Psychobiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
2Laboratory of Hormone Measurement, Department of Physiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
6Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
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Bruno Lobão Soares
1Postgraduate Program in Psychobiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
4National Institute of Science and Technology in Translational Medicine Natal, RN, Brazil;
5Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
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Nicole Leite Galvão-Coelho
1Postgraduate Program in Psychobiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
2Laboratory of Hormone Measurement, Department of Physiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil;
4National Institute of Science and Technology in Translational Medicine Natal, RN, Brazil;
7Department of Physiology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
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ABSTRACT

The incidence of major depression in adolescents, aged between 15 to 18 years, reaches approximately 14%. Usually, this disorder presents a recurrent way, without remission of symptoms even after several pharmacological treatments, persisting through adult life. Due to the relatively low efficacy of commercially available antidepressant, new pharmacological therapies are under continuous exploration. Recent evidence suggests that classic psychedelics, such as ayahuasca, produce rapid and robust antidepressant effects in treatment-resistant depression patients. In this study, we evaluated the potential of antidepressant effects of ayahuasca in a juvenile model of depression in a non-human primate, common marmoset (Callithrix jacchus). The model induces depressive-like symptoms by chronic social isolation (60 days) and antidepressant effects monitoring included fecal cortisol, body weight, and behavioral parameters. The animals presented hypocortisolemia and the recovery of cortisol to baseline levels started already at 24h after the ingestion of ayahuasca, but not the vehicle. Moreover, in males, ayahuasca, and not the vehicle, reduced the scratching, a stereotypic behavior, and increased the feeding. Ayahuasca also improving body weight to baseline levels in male and female common marmosets. The behavioral response induced by ayahuasca shows long effect, lasting 14 days. Therefore, for this translational animal model of juvenile depression, it could be proposed that ayahuasca treatment presented more notable antidepressant effects than tricyclic antidepressant nortriptyline, investigated by our group, using this same protocol in an anterior study. Ayahuasca produced faster and more durable effect on reversion of physiological changes and depressive-like symptoms. Therefore, the results found for ayahuasca treatment corroborates in the validation of this substance as an effective antidepressant drug and encourages the return of studies with psychedelic drugs in the treatment of humor disorders, including adolescents with early-age depression.

  • Abbreviations

    BL
    Baseline
    IC
    Isolated context
    VE
    Vehicle Treatment
    PH
    Pharmacological treatment
    tPE
    tardive-Pharmacological Effects
    D1
    Day 1
    D2
    Day 2.
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    Posted January 25, 2018.
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    Acute antidepressant effect of ayahuasca in juvenile non-human primate model of depression
    Flávia Santos da Silva, Erick Allan dos Santos Silva, Geovan Menezes de Sousa Junior, Joao Paulo Maia-de-Oliveira, Vanessa de Paula Soares Rachetti, Draulio Barros de Araujo, Maria Bernardete Cordeiro de Sousa, Bruno Lobão Soares, Nicole Leite Galvão-Coelho
    bioRxiv 254268; doi: https://doi.org/10.1101/254268
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    Acute antidepressant effect of ayahuasca in juvenile non-human primate model of depression
    Flávia Santos da Silva, Erick Allan dos Santos Silva, Geovan Menezes de Sousa Junior, Joao Paulo Maia-de-Oliveira, Vanessa de Paula Soares Rachetti, Draulio Barros de Araujo, Maria Bernardete Cordeiro de Sousa, Bruno Lobão Soares, Nicole Leite Galvão-Coelho
    bioRxiv 254268; doi: https://doi.org/10.1101/254268

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