Acute iboga alkaloid effects on extracellular serotonin (5-HT) levels in nucleus accumbens and striatum in rats.

Ibogaine, its metabolite noribogaine, and the related compound 18-methoxycoronaridine (18-MC) have been claimed to reduce addiction in animal models, but their mechanisms are unclear. In awake female rats, ibogaine caused large increases in extracellular serotonin in the nucleus accumbens (up to 25-fold) and striatum (up to 10-fold), noribogaine produced moderate increases (up to 8-fold and 5-fold), and 18-MC had no effect. These results suggest that the serotonin system may not be essential for anti-addictive effects; ibogaine may both release and block reuptake of serotonin; its hallucinogenic effect may involve serotonin stimulation; and 18-MC likely lacks serotonin transporter affinity and is unlikely to be a hallucinogen.

Study at a glance

Abstract

The iboga alkaloid, ibogaine, its metabolite, noribogaine, and the congener, 18-methoxycoronaridine (18-MC) have all been claimed to have anti-addictive properties in animal models, but the mechanisms underlying these effects are unclear. Ibogaine and noribogaine were shown to have affinity for the serotonin transporter, and inhibition of serotonin reuptake has been proposed to be involved in their anti-addictive actions. It is not known yet if 18-MC also has this property. In vivo microdialysis and HPLC (microbore) were used to determine acute changes in extracellular serotonin levels in nucleus accumbens (NAC) and striatum (STR) after both i.p. (40 mg/kg for all drugs) and i.v. (1-10 mg/kg for ibogaine and noribogaine) drug administration in awake freely moving female Sprague-Dawley rats (250-275 g). After i.p. administration, ibogaine, noribogaine and 18-MC had very different effects on extracellular serotonin levels in both NAC and STR: ibogaine elicited large increases (up to 25-fold in NAC and 10- fold in STR), noribogaine produced moderate increases (up to 8-fold in NAC and 5-fold in STR), and 18-MC had no effect in either brain region. These and other data suggest that (1) the serotonergic system may not be an essential factor in the anti-addictive actions of these drugs; (2) ibogaine (or an unidentified metabolite) may release serotonin as well as inhibit its reuptake; (3) stimulation of the ascending serotonergic system may mediate ibogaine's hallucinogenic effect; and (4) 18-MC probably has no affinity for the serotonin transporter, and is unlikely to be a hallucinogen.