Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Aconitum Alkaloid Songorine Exerts Potent Gamma-aminobutyric Acid A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety Without Adverse Sedative or Psychomotor Effects in the Rat

Zsolt Kristóf Bali
ORCID logo ,
Nóra Bruszt
,
Zsombor Kőszegi
,
Lili Veronika Nagy
ORCID logo ,
Tamás Atlasz
,
Péter Kovács
,
Dezső Csupor
,
Boglárka Csupor-Löffler
,
István Hernádi
* ORCID logo
Version 1 : Received: 27 August 2022 / Approved: 30 August 2022 / Online: 30 August 2022 (03:45:03 CEST)

A peer-reviewed article of this Preprint also exists.

Bali, Z.K.; Bruszt, N.; Kőszegi, Z.; Nagy, L.V.; Atlasz, T.; Kovács, P.; Csupor, D.; Csupor-Löffler, B.; Hernádi, I. Aconitum Alkaloid Songorine Exerts Potent Gamma-Aminobutyric Acid-A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety without Adverse Sedative or Psychomotor Effects in the Rat. Pharmaceutics 2022, 14, 2067. Bali, Z.K.; Bruszt, N.; Kőszegi, Z.; Nagy, L.V.; Atlasz, T.; Kovács, P.; Csupor, D.; Csupor-Löffler, B.; Hernádi, I. Aconitum Alkaloid Songorine Exerts Potent Gamma-Aminobutyric Acid-A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety without Adverse Sedative or Psychomotor Effects in the Rat. Pharmaceutics 2022, 14, 2067.

Abstract

Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0-3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator refer-ence compound diazepam (1.0-5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

Keywords

GABA-A receptors; in vivo electrophysiology; microiontophoresis; vigilance; anxiety; behavioral pharmacology; diterpene alkaloids; picrotoxin; saclofen; songorine

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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