Responses of the extrapyramidal and limbic substance P systems to ibogaine and cocaine treatments

• Published in: European journal of pharmacology Vol. 390; no. 1; pp. 119 - 126
• Main Authors: Alburges, Mario E, Ramos, Brian P, Bush, Lloyd, Hanson, Glen R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.02.2000; Elsevier
• Subjects: Animals; Biological and medical sciences; Cocaine; Cocaine - administration & dosage; Cocaine - pharmacology; Dopamine; Dopamine Antagonists - pharmacology; Dopamine D2 Receptor Antagonists; Dopamine Uptake Inhibitors - administration & dosage; Dopamine Uptake Inhibitors - pharmacology; Dose-Response Relationship, Drug; Drug abuse; Drug addictions; Extrapyramidal Tracts - drug effects; Extrapyramidal Tracts - metabolism; Ibogaine; Ibogaine - administration & dosage; Ibogaine - pharmacology; Immunohistochemistry; Injections, Intraperitoneal; Limbic System - drug effects; Limbic System - metabolism; Male; Medical sciences; Methamphetamine; Neurotensin; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - antagonists & inhibitors; Substance P; Substance P - metabolism; Substance P - physiology; Toxicology; Drug abuse; Dopamine; Substance P; Methamphetamine; Cocaine; Neurotensin; Ibogaine; Intraperitoneal administration; Rat; Pathogenesis; Psychotropic; Peptide hormone; Limbic system; Frontal cortex; Neuropeptide; Medicinal plant; Ester; Drug of abuse; Phytotherapy; Mechanism of action; Drug addiction; CNS stimulant; Pharmacognosy; Rodentia; Tissue specificity; Corpus striatum; Biological activity; Nucleus accumbens; Vertebrata; Mammalia; Locus niger; Animal; Plant origin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00919-X

Ibogaine is an indolamine found in the West Africa shrub, Tabernanthe iboga, and has been proposed for the treatment of addiction to central nervous system (CNS) stimulants such as cocaine and amphetamine. The mechanism of ibogaine action and its suitability as a treatment for drug addiction still remains unclear. Since previous studies demonstrated differential effects of stimulants of abuse (amphetamines) on neuropeptide systems such as substance P, we examined the impact of ibogaine and cocaine on extrapyramidal (striatum and substantia nigra) and limbic (nucleus accumbens and frontal cortex) substance P-like immunoreactivity. Ibogaine and cocaine treatments altered substance P systems by increasing striatal and nigral substance P-like immunoreactivity concentration 12 h after the last drug treatment. However, substance P-like immunoreactivity content was not significantly increased in nucleus accumbens after treatment with either drug. The ibogaine- and cocaine-induced increases in substance P-like immunoreactivity in striatum and substantia nigra were blocked by coadministration of selective dopamine D 1 receptor antagonist (SCH 23390; R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride) or dopamine D 2 receptor antagonist (eticlopride; S(−)-3-Chloro-5-ethyl- N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxy-benzamide hydrochloride). Most of the responses by substance P systems to ibogaine administration resembled those caused by cocaine, except in cortical tissue where multiple administration of cocaine, but not ibogaine increased substance P-like immunoreactivity. These data suggest that substance P systems may contribute to the effects of ibogaine and cocaine treatment.