Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice

N-methyl-D-aspartate receptor (NMDAR) modulators induce rapid and sustained antidepressant like-activity in rodents through a molecular mechanism of action that involves the activation of Ca dependent signaling pathways. Moreover, ketamine, a global NMDAR antagonist is a potent, novel, and atypical...

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Vydáno v:	Frontiers in molecular neuroscience Ročník 11; s. 456
Hlavní autoři:	Pochwat, Bartłomiej, Szewczyk, Bernadeta, Kotarska, Katarzyna, Rafało-Ulińska, Anna, Siwiec, Marcin, Sowa, Joanna E., Tokarski, Krzysztof, Siwek, Agata, Bouron, Alexandre, Friedland, Kristina, Nowak, Gabriel
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland Frontiers Research Foundation 12.12.2018 Frontiers Media Frontiers Media S.A
Témata:	AKT protein Antidepressants Brain-derived neurotrophic factor Calcium (intracellular) Calcium imaging Calcium influx Calcium signalling Clinical trials Cognitive ability Cortex (frontal) Corticosterone depression Dizocilpine Drug dosages Enzyme inhibitors Glutamic acid receptors hyperforin Ketamine lanicemine Life Sciences Mental depression N-Methyl-D-aspartic acid receptors Neurobiology Neuroimaging Neuromodulation Neurons and Cognition Neuroscience Neurosciences NMDA - receptor Pattern recognition Pharmaceutical sciences Pharmacy Psychiatry Psychotropic drugs Studies Synapsin I Transient receptor potential proteins TRPC 6 Western blotting Poland TRPC 6 hyperforin depression ketamine lanicemine NMDA - receptor
ISSN:	1662-5099, 1662-5099
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Shrnutí:	N-methyl-D-aspartate receptor (NMDAR) modulators induce rapid and sustained antidepressant like-activity in rodents through a molecular mechanism of action that involves the activation of Ca dependent signaling pathways. Moreover, ketamine, a global NMDAR antagonist is a potent, novel, and atypical drug that has been successfully used to treat major depressive disorder (MDD). However, because ketamine evokes unwanted side effects, alternative strategies have been developed for the treatment of depression. The objective of the present study was to determine the antidepressant effects of either a single dose of hyperforin or lanicemine vs. their combined effects in mice. Hyperforin modulates intracellular Ca levels by activating Ca -conducting non-selective canonical transient receptor potential 6 channel (TRPC6) channels. Lanicemine, on the other hand, blocks NMDARs and regulates Ca dependent processes. To evaluate the antidepressant-like activity of hyperforin and lanicemine, a set of (behavioral) and methods (western blotting, Ca imaging studies, electrophysiological, and radioligand binding assays) was employed. Combined administration of hyperforin and lanicemine evoked long-lasting antidepressant-like effects in both naïve and chronic corticosterone-treated mice while also enhancing the expression of the synapsin I, GluA1 subunit, and brain derived neurotrophic factor (BDNF) proteins in the frontal cortex. In Ca imaging studies, lanicemine enhanced Ca influx induced by hyperforin. Moreover, compound such as MK-2206 (Akt kinase inhibitor) inhibited the antidepressant-like activity of hyperforin in the tail suspension test (TST). Hyperforin reversed disturbances induced by MK-801 in the novel object recognition (NOR) test and had no effects on NMDA currents and binding to NMDAR. Our results suggest that co-administration of hyperforin and lanicemine induces long-lasting antidepressant effects in mice and that both substances may have different molecular targets.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC6299069 Edited by: Boldizsar Czeh, University of Pécs, Hungary Reviewed by: Nashat Abumaria, Fudan University, China; Vivian B. Neis, Federal University of Santa Catarina, Brazil; Mira Jakovcevski, Max-Planck-Institut für Psychiatrie, Germany
ISSN:	1662-5099 1662-5099
DOI:	10.3389/fnmol.2018.00456