Effects of ibogaine, and cocaine and morphine after ibogaine, on ventral tegmental dopamine neurons.

Ibogaine, a plant-derived alkaloid, acutely excites dopamine neurons in the ventral tegmental area (VTA) of anesthetized rats, but this effect is not long-lasting. Pretreatment with ibogaine 6-8 hours or 19 hours before testing did not alter the spontaneous firing of VTA dopamine neurons or their response to morphine or cocaine. Because ibogaine's excitatory effect on these neurons is transient and does not persistently change how dopamine neurons respond to these drugs, other mechanisms must explain its proposed antiaddictive properties.

Study at a glance

Abstract

Ibogaine, an indole containing alkaloid, has been shown to reduce the rate of injection of morphine and cocaine in self-administration protocols. Since morphine- and cocaine-induced modulation of dopamine release is impulse dependent and essential for their reinforcing effects, disruption of dopamine neuronal activity by ibogaine could explain its purported 'antiaddictive' properties. Therefore, the present study was designed to determine: (1) the acute effects of ibogaine on the activity of VTA dopamine neurons, and (2) whether ibogaine pretreatment causes a persistent modification of the dopamine neuronal response to morphine and cocaine. Extracellular recordings in anesthetized animals found that intravenous ibogaine markedly excited VTA dopamine neuronal firing. However, ibogaine pretreatment (6-8 hr and 19 hr before) failed to alter either the spontaneous activity of VTA neurons, or the response of these dopamine neurons to morphine or cocaine. Thus, ibogaine's excitatory effect on VTA neurons is not long-lasting nor does it persistently alter cocaine- or morphine-induced changes in dopamine neuron impulse activity. Therefore, other mechanisms must be explored to account for the proposed antiaddictive properties of ibogaine.