Dopamine transporter occupancy by RTI-55, inhibition of dopamine transport and stimulation of locomotor activity
- Brookhaven National Lab., Upton, NY (United States); and others
Cocaine analogs such as RTI-55 (or {beta}CIT) with a higher affinity for the DAT are potentially useful as therapeutic drugs in cocaine abuse as well as for radiopharmaceutical use. Previously we showed that in mice RTI-55 (2 mg/Kg, i/p) reduced H-3 cocaine striatum-to-cerebellum ratios (St/Cb, {lg_bullet}) from 1.6 to 1.2 at 3 h after administration, with recovery by 12 h. In the present study we demonstrate a very similar time-course for transport {triangle} measured in striatal homo within 2 min of sacrifice. The maximum inhibition of uptake at about 1 h corresponded to about 80% of the control uptake rate, similar to the percent reduction in St/Cb. The time-course of the effect of this dose of RTI-55 on locomotor activity ({sq_bullet}) was complex, with a drop in the activity measure at 7 h, after a further injection of RTI-55, but activity remained higher than in saline controls. In spite of this complexity, which may be associated with stereotypies and/or exhaustion, the duration of increased activity is consistent with the duration of transporter blockade. These experiments support the notion that PET/SPECT measures of transporter occupancy accurately reflect transporter inhibition.
- OSTI ID:
- 563338
- Report Number(s):
- CONF-970602--
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 38; ISSN JNMEAQ; ISSN 0161-5505
- Country of Publication:
- United States
- Language:
- English
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