Iboga compounds reverse the behavioural disinhibiting and corticosterone effects of acute methamphetamine: Implications for their antiaddictive properties.
Pharmacology, biochemistry, and behavior – January 01, 2001
Source: PubMed
Summary
Compounds related to ibogaine show remarkable promise in reversing stimulant effects. Research explored if ibogaine and a synthetic derivative could counter methamphetamine's impact. Methamphetamine caused behavioral disinhibition and increased stress hormones. Significantly, pretreatment with these iboga compounds successfully reversed both the disinhibiting behavior and the stress hormone surge. This highlights a potent mechanism for their anti-addictive potential by mitigating how stimulants affect behavior and the body's stress response.
Abstract
This study investigated the effects of pretreatment with the putative antiaddictive compound, ibogaine (IBO), and its synthetic derivative, 18-methoxycoronaridine (18-MC), on the changes in behaviour in an elevated plus maze and the changes in corticosterone (CORT) produced by a low dose of methamphetamine (METH). In the elevated plus maze, the acute administration of METH (0.1 mg/kg ip, -20 min) produced an increase in both the number and the duration of open arm entries relative to saline (SAL)-treated controls. No effect of METH administration was observed on the total number of arm entries. These data indicated that METH alone produced either anxiolysis or behavioural disinhibition in this paradigm. More consistent with the latter possibility, the open arm behaviour of METH controls was associated with an increase in plasma levels of CORT, supporting a facilitatory role for CORT in this METH-induced effect. Pretreatment with both IBO and 18-MC (40 mg/kg ip, 19 h earlier) antagonized the behavioural disinhibiting effects of acute METH without altering locomotor activity. In addition, both iboga agents antagonized the increase in CORT produced by METH. These data provide insight into yet another potential mechanism through which iboga compounds may exert their antiaddictive effects, a reversal of the behavioural disinhibiting properties of stimulant drugs. Furthermore, these data indicate that this reversal is related to effects of iboga compounds on the stimulation of neuroendocrine systems by stimulant drugs.