IBOGAINE AND THE DOPAMINERGIC RESPONSE TO NICOTINE

There is increasing evidence that the rewarding effect of nicotine is mediated by the mesolimbic dopamine system. The first objective of thi s study was to examine the dopamine response to repeated IV infusions of nicotine. Using in vivo microdialysis in awake and freely moving ma le Sprague-Dawley rats, we demonstrated that IV nicotine infusions (0. 16 mg/kg or 0.32 mg/kg per infusion) produced increases in extracellul ar dopamine levels that were dose- and infusion order-dependent. Acute tolerance was evidenced by the smaller dopamine response produced by a second infusion of nicotine, administered 1 h after the first one. T olerance was reversible, since the dopamine response to a second infus ion of nicotine was unchanged when the interval between the infusions was increased to 3 h. Ibogaine, an alkaloid found in Tabernanthe iboga , is claimed to decrease smoking and to have an anti-nicotinic action. The second objective of this study was to establish whether this clai m has any neurochemical basis. Pretreatment with ibogaine (40 mg/kg, I P) 19 h prior to the first nicotine infusion (0.32 mg/kg per infusion) significantly attenuated the increase in extracellular dopamine level s induced by the nicotine infusions, suggesting that ibogaine may decr ease the rewarding effect of nicotine.