Journal of Ethnopharmacology 265 (2021) 113316 Available online 28 August 2020 0378-8741/© 2020 Elsevier B.V. All rights reserved. Calea zacatechichi Schltdl. (Compositae) produces anxiolytic- and antidepressant-like effects, and increases the hippocampal activity during REM sleep in rodents Lucía Martinez-Mota a , Adri´ an Cruz-Tavera a , Ana María Dorantes-Barr´ on b , Daniel Arrieta-B´ aez c , Ignacio Ramírez-Salado d , Manuel Alejandro Cruz-Aguilar d , Lilian Mayagoitia-Novales e , Julia Cassani f , Rosa Estrada-Reyes b, * a Laboratorio de Farmacología Conductual, Direcci´ on de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ram´ on de La Fuente Mu˜ niz, Calzada M´ exico- Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de M´ exico, Mexico b Laboratorio de Fitofarmacología, Direcci´ on de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ram´ on de La Fuente Mu˜ niz, Calzada M´ exico- Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de M´ exico, Mexico c Instituto Polit´ ecnico Nacional, CNMN, Luis Enrique Erro S/n, Unidad Prof. Adolfo L´ opez Mateos, Gustavo A. Madero, 07738, Ciudad de M´ exico, Mexico d Laboratorio de Cronobiología y Sue˜ no, Direcci´ on de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ram´ on de La Fuente Mu˜ niz, Calzada M´ exico- Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de M´ exico, Mexico e Departamento de Etología, Direcci´ on de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ram´ on de La Fuente Mu˜ niz, Calzada M´ exico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, Ciudad de M´ exico, Mexico f Departamento de Sistemas Biol´ ogicos, Universidad Aut´ onoma Metropolitana, Unidad Xochimilco, Ciudad de M´ exico, 04960, Mexico A R T I C L E INFO Keywords: Calea zacatechichi Anxiety Depression Dreams Hippocampal gamma-band Brain oscillations Spectrum-EEG bands Chemical compounds studied in this article: Clomipramine hydrochloride (PubChem CID: 4336361) Butorphanol (PubChem CID: 24892126) Desipramine hydrochloride (PubChem CID: 65327) Diazepam (PubChem CID: 3016) Fluoxetine (PubChem CID: 62857) ABSTRACT Ethnopharmacological relevance: Calea zacatechichi is a plant with an extensive popular and ritual use in Mexico. In healthy volunteers, it induces well-being and tranquility senses, and facilitates superfcial stages of sleep. However, anxiolytic, and antidepressant-like effects and changes on the sleep-waking stages have not been explored. Aim: To determine anxiolytic and antidepressant-like effects of an aqueous extract of C. zacatechichi (CZ) in rodents and to analyze their effects on hippocampal activity in the rat sleep-waking cycle. Material and methods: CZ anxiolytic- and antidepressant-like effects were evaluated in several mice and rat behavioral paradigms. CZ effects on temporal distribution of sleep were described, and hippocampus EEG fre- quency patterns were analyzed during the sleep-waking cycle; absolute and relative powers were analyzed during Rapid Eye Movements (REM) and non-REM sleep stages. CZ chemical analysis was performed by UPLC- ESI-MS. Results: CZ produced specifc and robust anxiolytic- and antidepressant-like effects in mice and rats, similar to those of prototypical drugs, at doses ranging from 0.5 to 50 mg/kg. CZ at 100 mg/kg produced visible mild sedative effects in rats, associated with a signifcant increase in Slow Wave Sleep episodes during a 6 h recording, and enhanced fast frequencies of hippocampus (gamma-band:31–50 Hz) during REM sleep. Conclusion: Results could support the well-being and tranquility senses reported by healthy consumers, and to explain the oneiric content during dreams and some improvements in cognitive processes described by con- sumers. Anxiolytic- and antidepressant-like effects of this species, reported for frst time in this study could improve some aspects of mental health. 1. Introduction Calea zacatechichi, traditionally known as Zacatechichi, ‘thle-pela- kano’ or bitter-grass, has an extensive popular use in Mexico as an appetizer cholagogue, a cathartic anti-dysentery remedy, and as a sleep inductor (Díaz, 1976). This plant has been used by Chontal Indians during rituals to expand sensory perception and to receive “divine * Corresponding authorLaboratorio de Fitofarmacología, Direcci´ on de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ram´ on de la Fuente Mu˜ niz, Calzada M´ exico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, 14370, CDMX, Mexico. E-mail address: restrada@imp.edu.mx (R. Estrada-Reyes). Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm https://doi.org/10.1016/j.jep.2020.113316 Received 4 February 2020; Received in revised form 3 June 2020; Accepted 23 August 2020