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, Nóra Bruszt, Zsombor Kőszegi, Lili Veronika Nagy, Tamás Atlasz, Péter Kovács, Dezső Csupor, Boglárka Csupor-Löffler, István Hernádi
Author Information
Zsolt Kristóf Bali: Grastyán Endre Translational Research Centre, University of Pécs, 6 Ifjúság Str., H-7624 Pécs, Hungary. ORCID
Nóra Bruszt: Translational Neuroscience Research Group, Centre for Neuroscience, Szentágothai Research Centre, University of Pécs, 20 Ifjúság Str., H-7624 Pécs, Hungary.
Zsombor Kőszegi: Department of Experimental Zoology and Neurobiology, University of Pécs, 6 Ifjúság Str., H-7624 Pécs, Hungary. ORCID
Lili Veronika Nagy: Grastyán Endre Translational Research Centre, University of Pécs, 6 Ifjúság Str., H-7624 Pécs, Hungary. ORCID
Tamás Atlasz: Department of Experimental Zoology and Neurobiology, University of Pécs, 6 Ifjúság Str., H-7624 Pécs, Hungary. ORCID
Péter Kovács: Department of Experimental Zoology and Neurobiology, University of Pécs, 6 Ifjúság Str., H-7624 Pécs, Hungary.
Dezső Csupor: Department of Pharmacognosy, University of Szeged, 6 Eötvös Str., H-6720 Szeged, Hungary. ORCID
Boglárka Csupor-Löffler: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti Str., H-7624 Pécs, Hungary.
István Hernádi: Grastyán Endre Translational Research Centre, University of Pécs, 6 Ifjúság Str., H-7624 Pécs, Hungary. ORCID
Songorine (SON) is a diterpenoid alkaloid from 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 reference 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.
