(+)-Catharanthine and (-)-18-methoxycoronaridine induce antidepressant-like activity in mice by differently recruiting serotonergic and norepinephrinergic neurotransmission
European Journal of Pharmacology. 2023-01-01; 939: 175454
DOI: 10.1016/j.ejphar.2022.175454
Lire sur PubMed
1. Eur J Pharmacol. 2023 Jan 15;939:175454. doi: 10.1016/j.ejphar.2022.175454.
Epub 2022 Dec 19.
(+)-Catharanthine and (-)-18-methoxycoronaridine induce antidepressant-like
activity in mice by differently recruiting serotonergic and norepinephrinergic
neurotransmission.
Arias HR(1), De Deurwaerdère P(2), El-Kasaby A(3), Di Giovanni G(4), Eom S(5),
Lee JH(5), Freissmuth M(3), Chagraoui A(6).
Author information:
(1)Department of Pharmacology and Physiology, Oklahoma State University College
of Osteopathic Medicine, Tahlequah, OK, USA.
(2)Centre National de la Recherche Scientifique, Institut des Neurosciences
Intégratives et Cognitives d’Aquitaine, UMR, 5287, Bordeaux, France.
(3)Institute of Pharmacology and the Gaston H. Glock Research Laboratories for
Exploratory Drug Development, Center of Physiology and Pharmacology, Medical
University of Vienna, Vienna, Austria.
(4)Laboratory of Neurophysiology, Department of Physiology and Biochemistry,
Faculty of Medicine and Surgery, University of Malta, Msida, Malta, Neuroscience
Division, School of Biosciences, Cardiff University, Cardiff, United Kingdom.
(5)Department of Biotechnology, Chonnam National University, Gwangju, South
Korea.
(6)Department of Medical Biochemistry, Rouen University Hospital, CHU de Rouen,
France; Différenciation et Communication Neuroendocrine, Endocrine et Germinale
Laboratory, Institute for Research and Innovation in Biomedicine of Normandy
(IRIB), University of Rouen, INSERM 1239, 76000, Rouen, France. Electronic
address: .
The antidepressant-like activity of (+)-catharanthine and
(-)-18-methoxycoronaridine [(-)-18-MC] was studied in male and female mice using
forced swim (FST) and tail suspension tests (TST). The underlying molecular
mechanism was assessed by electrophysiological, radioligand, and functional
experiments. The FST results showed that acute administration (40 mg/kg) of
(+)-catharanthine or (-)-18-MC induces similar antidepressant-like activity in
male and female mice at 1 h and 24 h, whereas the TST results showed a lower
effect for (-)-18-MC at 24 h. Repeated treatment at lower dose (20 mg/kg)
augmented the efficacy of both congeners. The FST results showed that (-)-18-MC
reduces immobility and increases swimming times without changing climbing
behavior, whereas (+)-catharanthine reduces immobility time, increases swimming
times more markedly, and increases climbing behavior. To investigate the
contribution of the serotonin and norepinephrine transporters in the
antidepressant effects of (+)-catharanthine and (-)-18-MC, we conducted in vitro
radioligand and functional studies. Results obtained demonstrated that
(+)-catharanthine inhibits norepinephrine transporter with higher
potency/affinity than that for (-)-18-MC, whereas both congeners inhibit
serotonin transporter with similar potency/affinity. Moreover, whereas no
congener activated/inhibited/potentiated the function of serotonin receptor 3A
or serotonin receptor 3AB, both increased serotonin receptor 3A receptor
desensitization. Depletion of serotonin decreased the antidepressant-like
activity of both congeners, whereas norepinephrine depletion only decreased
(+)-catharanthine’s activity. Our study shows that coronaridine congeners induce
antidepressant-like activity in a dose- and time-dependent, and sex-independent,
manner. The antidepressant-like property of both compounds involves serotonin
transporter inhibition, without directly activating/inhibiting serotonin
receptors 3, while (+)-catharanthine also mobilizes norepinephrinergic
neurotransmission.
Copyright © 2022 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.ejphar.2022.175454
PMID: 36549498 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of competing interest All authors
have made substantial contributions to the preparation of the manuscript.
Furthermore, they have not only contributed to the writing of the final
manuscript but have given their permission for submission and publication in
European Journal of Pharmacology. The authors declare that they have no known
competing financial interests or personal relationships that could have appeared
to influence the work reported in this paper.