Galphimine B Modulates Synaptic Transmission on Dopaminergic Ventral Tegmental Area Neurons

Abstract

Galphimine B (GB) is a bioactive compound isolated from the plant Galphimia glauca Cav. (Malpighiaceae) and has been shown to have central nervous system depressant properties. In an earlier study, it was reported that both systemic and local administration of GB modified the extracellular spontaneous spiking activity in the ventral tegmental area (VTA) neurons. In the present study we analyzed the synaptic effects of this compound on dopaminergic neurons. Recordings were made in brain slices using intracellular and patch-clamp techniques, in dopaminergic (DA) VTA neurons. Spontaneous miniature excitatory postsynaptic currents (mEPSCs), excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic potentials (IPSPs) were recorded in control situation and after bath infusions of several concentrations of GB (1 microM-5 mM), GABA (1 nM-100 microM) and the GABA A blockers, picrotoxin (100 microM) and bicuculline (10 microM), and GABA B blocker saclofen (200 microM). GB administration reduced the frequency (p < 0.05) but not the amplitude of mESPCs. However, GABA (IC 50 = 645 nM) and GB (IC 50 = 174.5 microM) infusion significantly reduced the amplitude of stimuli induced EPSCs, Bicuculline (10 microM) co-administration only reduced GABA effects and did not modify the GB depressant action. Finally, isolated GABAergic IPSPs were modified by the addition of picrotoxin, but GB had no effect on these evoked synaptic responses. The present results indicate that GB modifies synaptic activity on dopaminergic VTA neurons by a non-GABAergic mechanism.

A comparison on the metabolic profiling of the Mexican anxiolytic and sedative plant Galphimia glauca four years later

“…The sedative activity of galphimines has been demonstrated using in vitro models (Prieto- Gómez et al, 2003) and the anxiolytic action of galphimines A, B and E were documented in mice (Herrera-Ruiz et al, 2006). Moreover, in a clinical study performed in patients with general anxiety, the anxiolytic effect from standardized preparations of Galphimia glauca administered to the patients, was clearly demonstrated (Herrera-Arellano et al, 2007).…”

New anxiolytic phytopharmaceutical elaborated with the standardized extract of Galphimia glauca

“…In general, G-B inhibits the activity of the mesencephalic dopaminergic pathways. Intracellular records in brain slices showed that G-B inhibits the excitatory postsynaptic potentials; this effect was similar to that produced by GABA and clonazepam (Prieto Gómez, et al, 2003). Nonetheless, the effect produced by G-B was not blocked by bicuculline, picrotoxin, or flumazenil, thus providing an action mechanism independent of the GABA-A receptor.…”

Interaction of the natural anxiolytic Galphimine-B with serotonergic drugs on dorsal hippocampus in rats

“…Some years ago, possible interaction was evaluated with the GABAergic system by means of electrophysiological records. Recordings in brain slices utilizing intracellular and patch-clamp techniques indicated that G-B modifies synaptic activity in dopaminergic VTA neurons by means of a non-GABAergic mechanism (Prieto-Gómez et al, 2003).…”

“…Through electrophysiological tests, it has been demonstrated that G-B possesses an inhibitory effect on dopaminergic neurons of Ventral tegmental area (VTA) in rats (Tortoriello et al, 1998). Apparently, such actions are not the result of interaction with the ␥-aminobutyric acid (GABA)ergic system (Prieto-Gómez et al, 2003). By means of a double-blind clinical trial, the extract of Galphimia glauca (standardized in 0.340 mg of G-B per dose) evidenced an important anxiolytic effect, similar to that produced by lorazepam (1 mg) in patients with Generalized anxiety disorder (GAD) (Herrera-Arellano et al, 2007).…”