Abstract
2β-Propanoyl-3β-(2-naphthyl)-tropane (WF-23) is a potent cocaine analog with activity at dopamine and serotonin transporters. The purpose of these experiments was to characterize the time course of effects of acute administration of WF-23 on spontaneous locomotion and biogenic amine transporters. Rats received injections i.p. with WF-23 (1 mg/kg), cocaine (30 mg/kg) or vehicle and locomotor activity was measured at various times postinjection. Animals were killed immediately after behavioral activity. Locomotor activity was significantly increased by WF-23 administration, reaching maximum at 4 hr and persisting for 24 hr. Cocaine-elicited elevations in locomotor activity occurred only at the earliest times. WF-23 decreased DA transporter binding in striatal membranes ([125I]RTI-55 binding), with >50% loss in binding for up to 49 hr postinjection. WF-23 increased the Kd of the high affinity site, with no effect on Bmax. Cocaine depressed binding (20%) only at the earliest times. WF-23 decreased levels of [3H]WIN 35,428 binding sites up to 95% of control in both dorsal and ventral striatum with a similar time-course when assessed autoradiographically. WF-23 also reduced [3H]citalopram binding to serotonin transporter sites throughout the brain. The slow onset and very long duration of action of WF-23, taken together with its actions at dopamine and serotonin transporters, suggest a potential role for treatment of disorders characterized by their involvement of these neural systems.
Footnotes
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Send reprint requests to: Dr. Linda J. Porrino, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157.
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↵1 This work was supported by NIDA Grants P50 DA06634, DA 07246 (J.B.D.) and DA06301 (H.M.L.D.).
- Abbreviations:
- WF-23
- (2β-propanoyl-3β-(2-naphthyl)-tropane)
- DA
- dopamine
- 5HT
- serotonin
- NAc
- nucleus accumbens
- LAAM
- L-α-acetylmethadol
- Received September 18, 1997.
- Accepted February 16, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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