Lobeline attenuates d-methamphetamine self-administration in rats

alpha -lobeline inhibits d-amphetamine-evoked dopamine release from striata l slices in vitro, appearing to reduce the cytosolic pool of dopamine avail able for reverse transport by the dopamine transporter. Based on this neuro chemical mechanism of action, the present study determined if lobeline decr eases d-methamphetamine self-administration. Rats were surgically implanted with jugular catheters and were trained to lever press on a fixed ratio 5 schedule for intravenous d-methamphetamine (0.05 mg/kg/infusion). To assess the specificity of the effect of lobeline, another group of rats was train ed to lever press on a fixed ratio 5 schedule for sucrose reinforcement. Pr etreatment of rats with lobeline (0.3-3.0 mg/kg, 15 min prior to the sessio n) decreased responding for both d-methamphetamine and sucrose reinforcemen t. Following repeated lobeline (3.0 mg/kg) administration, tolerance develo ped to the decrease in responding for sucrose; however, the lobeline-induce d decrease in responding for d-methamphetamine persisted. Furthermore, the lobeline-induced decrease in responding for d-methamphetamine was not surmo unted by increasing the unit dose of d-methamphetamine, These results sugge st that lobeline produces a nonspecific rate suppressant effect following a cute administration, to which tolerance develops following repeated adminis tration. Importantly, the results also suggest that repeated administration of lobeline specifically decreases responding for d-methamphetamine in a n oncompetitive manner. Thus, lobeline may be an effective, novel pharmacothe rapy for d-methamphetamine abuse.