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.