Brain Res 1999 Feb 6;818(1):96-104
Differential responses by neurotensin systems in extrapyramidal and limbic
structures to ibogaine and {*filter*}.
Alburges ME, Hanson GR
Department of Pharmacology and Toxicology, College of Pharmacy, University of
Utah, 112 Skaggs
Hall, Salt Lake City, UT 84112, USA
[Record supplied by publisher]
Ibogaine (Endabuse) is a psychoactive indole alkaloid found in the West African
shrub, Tabernanthe
iboga. This drug interrupts {*filter*} and amphetamine abuse and has been proposed
for treatment of
{*filter*}ion to these stimulants. However, the mechanism of action that explains
its pharmacological
properties is unclear. Since previous studies demonstrated differential effects
of psychotomimetic
{*filter*} ({*filter*} and methamphetamine) on neuropeptides such as neurotensin (NT),
the present study
was designed to determine: (1) the effects of ibogaine on striatal, nigral,
cortical, and accumbens
neurotensin-like immunoreactivity (NTLI); (2) the effects of selective dopamine
antagonists on
ibogaine-induced changes in NT concentrations in these brain areas; and (3) the
effects of ibogaine
pretreatment on {*filter*}-induced changes in striatal, nigral, cortical and
accumbens NTLI content.
Ibogaine treatments profoundly affected NT systems by increasing striatal,
nigral, and accumbens
NTLI content 12 h after the last drug administration. In contrast, NTLI
concentrations were not
significantly increased in the frontal cortex after ibogaine treatment. The
ibogaine-induced increases in
NTLI in striatum, nucleus accumbens and substantia nigra were blocked by
coadministration of the s
elective D1 receptor antagonist, SCH 23390. The D2 receptor antagonist,
eticlopride, blocked the
ibogaine-induced increase in nigral NTLI, but not in striatum and nucleus
accumbens. Ibogaine
pretreatment significantly blocked the striatal and nigral increases of NTLI
resulting from a single
{*filter*} administration. Whereas many of the responses by NT systems to ibogaine
resembled those
which occur after {*filter*}, there were also some important differences. These
data suggest that NT
may contribute to an interaction between ibogaine and the DA system and may
participate in the
pharmacological actions of this drug. Copyright 1999 Elsevier Science B.V

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