Ibogaine enhances the expression of locomotor sensitization in rats chronically treated with cocaine.

Pretreatment (19 h) with the putative antiaddictive agent, ibogaine, has been shown previously to potentiate cocaine-induced locomotion in rats. The present study demonstrates that the magnitude of this effect of ibogaine is dependent on the previous cocaine history of the animal, on the time following ibogaine treatment, and on the number of ibogaine treatments. Compared to rats with no previous cocaine experience, ibogaine pretreatment (40 mg/kg, IP, 19 h earlier) markedly enhanced the expression of locomotor sensitization in response to a cocaine challenge injection (7.5 mg/kg) in rats that were chronically treated with cocaine (15 mg/ kg, IP, daily for 5 days). Tolerance to cocaine-induced locomotor sensitization appeared to occur in vehicle-pretreated chronic cocaine controls. Following a second series of identical treatments (beginning 3-4 days after the initial treatment series), locomotor responding to the cocaine challenge was further enhanced by a second ibogaine injection in chronically cocaine-treated animals. Twenty-four hours later, when animals were challenged again with cocaine in the absence of any further ibogaine pretreatment, the effect of ibogaine had dissipated. Consistent with previous studies from this laboratory, these data demonstrate that ibogaine can enhance sensitivity to the psychomotor stimulant effect of cocaine. The results of the present study further indicate that the extent of this effect depends on the animal's history of exposure to both ibogaine and cocaine.