Ibogaine antagonizes cocaine-induced locomotor stimulation in mice

Henry Sershen, Audrey Hashim, L. Hársing, Abel Lajtha

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Abstract

Ibogaine (40 mg/kg i.p.), when given 2 hours before an acute injection of cocaine (25 mg/kg s.c.) to C57BL/6 mice, reduced the cocaine-induced locomotor stimulation. Such stimulation was also reduced in the ibogaine-treated mice when a second injection of cocaine was given 24 hr later. Thus, the reduction in locomotor activity was not just the short-term depression of locomotor activity seen after ibogaine administration. When mice were given a daily injection of cocaine for 3 days and ibogaine was given after the cocaine injection on day 3, and again on day 4, cocaine-induced locomotor activity was reduced three hours later on day 4. On days 5 and 9 of the cocaine administration, with no further ibogaine treatment ambulatory counts were still lower in the ibogaine-pretreated mice. Locomotor stimulation induced by amphetamine (10 mg/kg) was not affected by ibogaine. An acute injection of ibogaine resulted in a transient increase in turnover of dopamine, as indicated by the increase in the ratio of metabolites of the dopamine to dopamine, followed by a decrease in the metabolites in striatum and frontal cortex 24 hr later. In vivo treatment with ibogaine did not affect the binding of [3H]WIN 35,248 to the cocaine binding site in striatal tissue measured in vitro. In addition, ibogaine added in vitro had a weak affinity to the WIN 35,248 binding site (IC50 for cocaine = 120 nM and for ibogaine = 1,500 nM). The results suggest that ibogaine may have induced a selective change in the dopaminergic system that results in a decrease in responsiveness to cocaine that persisted for at least 1 week.

Original languageEnglish
Pages (from-to)1079-1086
Number of pages8
JournalLife Sciences
Volume50
Issue number15
DOIs
Publication statusPublished - 1992

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Ibogaine
Cocaine
Locomotion
Injections
Dopamine
Metabolites
Binding Sites
Corpus Striatum
Frontal Lobe
Amphetamine
Inbred C57BL Mouse

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ibogaine antagonizes cocaine-induced locomotor stimulation in mice. / Sershen, Henry; Hashim, Audrey; Hársing, L.; Lajtha, Abel.

In: Life Sciences, Vol. 50, No. 15, 1992, p. 1079-1086.

Research output: Contribution to journalArticle

Sershen, Henry ; Hashim, Audrey ; Hársing, L. ; Lajtha, Abel. / Ibogaine antagonizes cocaine-induced locomotor stimulation in mice. In: Life Sciences. 1992 ; Vol. 50, No. 15. pp. 1079-1086.
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