Ibogaine and a total alkaloidal extract of Voacanga africana modulate neuronal excitability and synaptic transmission in the rat parabrachial nucleus in vitro.

Ibogaine, a natural alkaloid from Voacanga africana, reduces withdrawal symptoms and craving in drug addiction. Its cellular mechanisms were investigated in parabrachial nucleus neurons using patch-recording techniques. Ibogaine and the plant extract dose-dependently and reversibly suppress excitatory synaptic currents, with ibogaine having an ED50 of 5 microM and the extract 170 micrograms/ml. At higher concentrations, they depolarize neurons, increase firing rate, and raise input resistance. These effects are blocked by the dopamine receptor antagonist haloperidol. The findings indicate ibogaine and the extract alter neuronal excitability and synaptic transmission through dopaminergic and glutamatergic processes, with the extract being about one-hundredth as active as ibogaine.

Study at a glance

Abstract

Ibogaine is a natural alkaloid of Voacanga africana that is effective in the treatment of withdrawal symptoms and craving in drug addicts. As the synaptic and cellular basis of ibogaine's actions are not well understood, this study tested the hypothesis that ibogaine and Voacanga africana extract modulate neuronal excitability and synaptic transmission in the parabrachial nucleus using the nystatin perforated patch-recording technique. Ibogaine and Voacanga africana extract dose dependently, reversibly, and consistently attenuate evoked excitatory synaptic currents recorded in parabrachial neurons. The ED50 of ibogaine's effect is 5 microM, while that of Voacanga africana extract is 170 micrograms/ml. At higher concentrations, ibogaine and Voacanga africana extract induce inward currents or depolarization that are accompanied by increases in evoked and spontaneous firing rate. The depolarization or inward current is also accompanied by an increase in input resistance and reverses polarity around 0 mV. The depolarization and synaptic depression were blocked by the dopamine receptor antagonist haloperidol. These results indicate that ibogaine and Voacanga africana extract 1) depolarize parabrachial neurons with increased excitability and firing rate; 2) depress non-NMDA receptor-mediated fast synaptic transmission; 3) involve dopamine receptor activation in their actions. These results further reveal that the Voacanga africana extract has one-hundredth the activity of ibogaine in depressing synaptic responses. Thus, ibogaine and Voacanga africana extract may produce their central effects by altering dopaminergic and glutamatergic processes.