IBOGAINE AND A TOTAL ALKALOIDAL EXTRACT OF VOACANGA-AFRICANA MODULATENEURONAL EXCITABILITY AND SYNAPTIC TRANSMISSION IN THE RAT PARABRACHIAL NUCLEUS IN-VITRO

Ibogaine is a natural alkaloid of Voacanga africana that is effective in the treatment of withdrawal symptoms and craving in drug addicts. A s the synaptic and cellular basis of ibogaine's actions are not well u nderstood, this study tested the hypothesis that ibogaine and Voacanga africana extract modulate neuronal excitability and synaptic transmis sion in the parabrachial nucleus using the nystatin perforated patch-r ecording technique. Ibogaine and Voacanga africana extract dose depend ently, reversibly, and consistently attenuate evoked excitatory synapt ic currents recorded in parabrachial neurons. The ED50 of ibogaine's e ffect is 5 mu M, while that of Voacanga africana extract is 170 mu g/m l. At higher concentrations, ibogaine and Voacanga africana extract in duce inward currents or depolarization that are accompanied by increas es in evoked and spontaneous firing rate. The depolarization or inward current is also accompanied by an increase in input resistance and re verses polarity around 0 mV. The depolarization and synaptic depressio n were blocked by the dopamine receptor antagonist haloperidol. These results indicate that ibogaine and Voacanga africana extract 1) depola rize 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 f urther 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 al tering dopaminergic and glutamatergic processes. (C) 1997 Elsevier Sci ence Inc.