Evidence for roles of kappa-opioid and NMDA receptors in the mechanism of action of ibogaine.
Ibogaine, a putatively anti-addictive alkaloid, binds to kappa-opioid and NMDA receptors. In the present study we investigated the roles of kappa-opioid and NMDA actions in mediating ibogaine's (40 mg/kg, i.p.) behavioral and neurochemical effects in rats. A combination of a kappa-opioid antagonist (norbinaltorphimine, 10 mg/kg, s.c.) and a NMDA agonist (NMDA, 20 mg/kg, i.p.) partially prevented ibogaine-induced inhibition of intravenous morphine self-administration and ibogaine-induced antagonism of morphine-induced locomotor stimulation. The combination, as well as norbinaltorphimine and NMDA alone, blocked the acute effects of ibogaine on dopamine release and metabolism in the striatum. The data suggest that both kappa-opioid agonist and NMDA antagonist actions of ibogaine contribute to its putative anti-addictive effects.
Glick
S D
SD
Department of Pharmacology and Neuroscience, Albany Medical College, NY 12208, USA. sglick@ccgateway.amc.edu
Maisonneuve
I M
IM
Pearl
S M
SM
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007050:Ibogaine / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D012646:Self Administration; D019966:Substance-Related Disorders
D009292:Narcotic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D007050:Ibogaine; D009271:Naltrexone; D016202:N-Methylaspartate; D009020:Morphine; D004298:Dopamine