Iboga compounds reverse the behavioural disinhibiting and corticosterone effects of acute methamphetamine: Implications for their antiaddictive properties

This study investigated the effects of pretreatment with the putative antia ddictive compound, ibogaine (IBO), and its synthetic derivative, 18-methoxy coronaridine (18-MC), on the changes in behaviour in an elevated plus maze and the changes in corticosterone (CORT) produced by a low dose of methamph etamine (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 d uration of open arm entries relative to saline (SAL)-treated controls. No e ffect of METH administration was observed on the total number of arm entrie s. These data indicated that METH alone produced either anxiolysis or behav ioural disinhibition in this paradigm. More consistent with the latter poss ibility, the open arm behaviour of METH controls was associated with an inc rease 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 an tagonized the increase in CORT produced by METH. These data provide insight into yet another potential mechanism through which iboga compounds may exe rt 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 neu roendocrine systems by stimulant drugs. (C) 2001 Elsevier Science Inc. All rights reserved.