Characteristics of [³H]GBR 12935 Binding in the Human and Rat Frontal Cortex

Abstract: Binding characteristics of the selective dopamine uptake inhibitor [³H]GBR 12935 have been described for the striatum but not for the frontal cortex. We have developed assay conditions for quantifying [³H]GBR 12935 binding in the frontal cortex. In both the rat and human frontal cortex, the assay required four times more tissue (8 mg/ml) than in the striatum (2 mg/ml).[³H]GBR 12935 binding in the frontal is complex, as it involves multiple binding sites. The high‐affinity binding site is sodium dependent and is inhibited by sodium. In human but not in rat frontal cortex, addition of K⁺ reversed the sodium inhibition. The pharmacological profile of the high‐affinity [³H]GBR 12935 binding site is consistent with that of the dopamine transporter, because drugs with the most selective dopamine reuptake blocking activities are the most potent displacers of [³H]GBR 12935 binding. There is a positive correlation between the rat and human inhibitory constants, a finding indicating that there are similar pharmacological profiles across at least these two species. Rats with a 6‐hydroxydopamine lesion had a 47% decrease in number of [³H]GBR 12935 binding sites, a result indicating that at least a portion of these sites had been on presynaptic dopamine terminals.