Effects of ibogaine, and cocaine and morphine after ibogaine, on ventral tegmental dopamine neurons.
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.
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Department of Pharmacology, University of Arizona, College of Medicine, Tucson 85724, USA.
Dillon
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Ali
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D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D007050:Ibogaine / Q000008:administration & dosage / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects*
D007050:Ibogaine; D009020:Morphine; D003042:Cocaine; D004298:Dopamine