Pretreatment with the putative anti-addictive drug, ibogaine, increases the potency of cocaine to elicit locomotor responding: a study with acute andchronic cocaine-treated rats

Rationale: Results of single-dose studies suggest that the effects of pretr eatment with the putative an-ti-addictive compound, ibogaine, on drug-induc ed locomotor behavior depends on the previous drug history of the animal. O bjectives: To compare the effects of ibogaine pretreatment on the dose-loco motor response function for cocaine in rats treated chronically with either saline or cocaine. Methods: Rats were chronically treated with either coca ine (15 mg/kg, IP, once daily for 5 days, followed by 2 week withdrawal) or saline. Ibogaine (40 mg/kg, IP) or vehicle was administered and 19 h later , a cocaine dose-locomotor response test was conduct ed (0, 5, 10, 20 and 4 0 mg/kg, IP). Results: Chronic cocaine administration augmented the locomot or response to cocaine in chronic cocaine-treated rats, compared to acutely treated controls. Ibogaine pretreatment enhanced the locomotor effects of cocaine in both chronic and acute cocaine groups. Furthermore, due to the s hape of the dose-response curve, in chronic cocaine but not in acute cocain e rats, ibogaine pretreatment enhanced the locomotor response to 5 and 10 m g/kg cocaine while de creasing the locomotor response to 40 mg/kg cocaine. Conclusions: These data demonstrate definitively that ibogaine can enhance sensitivity to the locomotor stimulant effects of cocaine, an effect which depends, in part, on the previous cocaine history of the animal.