Discrimination of Multiple [3H]5‐Hydroxytryptamine Binding Sites by the Neuroleptic Spiperone in Rat Brain

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Abstract
Certain neuroleptic drugs, e.g., spiperone and (+) butaclamol, can discriminate between 2 populations of [3H]5-hydroxytryptamine ([3H]5-HT) binding sites in rat brain. The butyrophenone neuroleptic spiperone showed the greatest selectivity for these 2 binding sites, having at least a 3000-fold difference between its Kd (2-12 nM vs. 35,000 nM) for the high- and low-affinity sites, respectively. Inhibition of [3H]5-HT binding by spiperone in rat frontal cortex and corpus striatum yielded distinctly biphasic inhibition curves with Hill slopes significantly less than unity. A nonlinear regression analysis of inhibition was consistent with a 2-site model in each brain region. In the frontal cortex the high-affinity neuroleptic sites comprised about 60% of the total [3H]5-HT binding sites; in the corpus striatum they accounted for only 20% of the sites. The saturations of [3H]5-HT binding assayed in the absence or presence of 1 .mu.M-spiperone (a concentration that completely blocks the high-affinity site while having minimal activity at the low-affinity site) revealed a parallel shift in the Scatchard plot with no change in the Kd of [3H]5-HT, but a significant decrease (64% in frontal cortex of 28% in corpus striatum) in the number of specific binding sites. At least 2 populations of [3H]5-HT binding sites having a differential regional distribution apparently existing in rat brain.