Modulation of methamphetamine's locomotor stimulation and self-administration by JHW 007, an atypical dopamine reuptake blocker

摘要

JHW 007 [N-(n-butil)-3a-[bis(4'-fluorophenil)methoxi]-tropane] belongs to the family of N-substituted benztropine (BZT) analogs, atypical dopamine transporter (DAT) blockers that are able to strongly modulate cocaine- and amphetamine-related behavior. In the present study, we tested in rats the ability of JHW 007 to alter the stimulant and reinforcing properties of methamphetamine (METH) using locomotor activity, fixed ratio and progressive ratio (PR) self-administration tests. The results showed that JHW 007 attenuated METH-induced locomotor stimulation in a dose-dependent manner and had no stimulant effects when administered alone. The BZT analog, given as a pre-treatment, attenuated METH self-administration without affecting responding for sucrose. In the PR tests JHW 007 produced an increase of the breaking point achieved for both METH- and sucrose self-administration, suggesting that the ability of the BZT analog to reduce self-administration may be linked to its ability to enhance the reinforcing properties of METH. Taken together, these data suggest that DAT inhibition with a high affinity blocker such as JHW 007 can exert differential effects on METH-associated behaviors, reducing METH-induced motor stimulation but augmenting METH's reinforcing effects.