Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice.
Bartłomiej Pochwat, Bernadeta Szewczyk, Katarzyna Kotarska, Anna Rafało-Ulińska, Marcin Siwiec, Joanna E Sowa, Krzysztof Tokarski, Agata Siwek, Alexandre Bouron, Kristina Friedland, Gabriel Nowak
Frontiers in Molecular Neuroscience 2018 DOI: 10.3389/fnmol.2018.00456 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice, including naive and chronic corticosterone-treated mice |
| Interventions | Hyperforin Lanicemine MK-2206 MK-801 |
| Measures | tail suspension test (TST), novel object recognition (NOR) test, western blotting, Ca2+ imaging, electrophysiological assays, radioligand binding assays |
| Topics | Depression Ketamine |
| Keywords | Nmda - receptor Trpc 6 Hyperforin Lanicemine |
| Key points | Co-administration of hyperforin and lanicemine produced long-lasting antidepressant-like effects in naive and chronic corticosterone-treated mice and increased synapsin I, GluA1, and BDNF protein expression in the frontal cortex. Lanicemine enhanced hyperforin-induced calcium influx, and the Akt inhibitor MK-2206 blocked hyperforin's antidepressant-like activity in the tail suspension test. Hyperforin reversed MK-801-induced deficits in novel object recognition but did not affect NMDA currents or NMDA receptor binding, suggesting the two compounds act on different molecular targets. |
Abstract
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 Ca2+ 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 Ca2+ levels by activating Ca2+-conducting non-selective canonical transient receptor potential 6 channel (TRPC6) channels. Lanicemine, on the other hand, blocks NMDARs and regulates Ca2+ dependent processes. To evaluate the antidepressant-like activity of hyperforin and lanicemine, a set of in vivo (behavioral) and in vitro methods (western blotting, Ca2+ 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 Ca2+ imaging studies, lanicemine enhanced Ca2+ 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.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
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and 10 more in the library