LONG-ACTING BLOCKADE OF BIOGENIC-AMINE TRANSPORTERS IN RAT-BRAIN BY ADMINISTRATION OF THE POTENT NOVEL TROPANE 2-BETA-PROPANOYL-3-BETA-(2-NAPHTHYL)-TROPANE

2 beta-Propanoyl-3 beta-(2-naphthyl)-tropane (WF-23) is a potent cocai ne analog with activity at dopamine and serotonin transporters. The pu rpose of these experiments was to characterize the lime course of effe cts of acute administration of WF-23 on spontaneous locomotion and bio genic amine transporters. Rats received injections i.p, with WF-23 (1 mg/kg), cocaine (30 mg/kg) or vehicle and locomotor activity was measu red at various times postinjection. Animals were killed immediately af ter behavioral activity. Locomotor activity was significantly increase d by WF-23 administration, reaching maximum at 4 hr and persisting for 24 hr. Cocaine-elicited elevations in locomotor activity occurred onl y at the earliest times. WF-23 decreased DA transporter binding in str iatal membranes ([I-125]RTI-55 binding), with >50% loss in binding for up to 49 hr postinjection. WF-23 increased the K-d of the high affini ty site, with no effect on B-max. Cocaine depressed binding (20%) only at the earliest times. WF-23 decreased levels of [H-3]WIN 35,428 bind ing sites up to 95% of control in both dorsal and ventral striatum wit h a similar time-course when assessed autoradiographically. WF-23 also reduced [H-3]citalopram binding to serotonin transporter sites throug hout the brain. The slow onset and very long duration of action of WF- 23, taken together with its actions at dopamine and serotonin transpor ters, suggest a potential role for treatment of disorders characterize d by their involvement of these neural systems.