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 μM - 5 mM), GABA (1 nM - 100 μM) and the GABA_A blockers, picrotoxin (100 μM) and bicuculline (10 μM), and GABA_B blocker saclofen (200 μM). GB administration reduced the frequency (p < 0.05) but not the amplitude of mESPCs. However, GABA (IC₅₀ = 645 nM) and GB (IC₅₀ = 174.5 μM) infusion significantly reduced the amplitude of stimuli induced EPSCs, Bicuculline (10 μM) 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.

Galphimine B - ventral tegmental area - dopaminergic neurons - synaptic transmission - synaptic currents - GABA - Galphimia glauca - Malpighiaceae

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