Distinct Binding Patterns of [3H]Raclopride and [3H]Spiperone at Dopamine D2 Receptors in vivo in Rat Brain. Implications for Pet Studies

Abstract

Positron emission tomography studies (PET) on dopamine (DA) D₂ receptors of schizophrenics provided conflicting data, perhaps because the ligands generally used, raclopride (RAC) and spiperone (SPI), did not label the same sites. In this study, we found that the in vivo binding characteristics of ³H]RAC and of ³H]SPI in rat brain, differed in many ways. 1) ³H]RAC labeled twice as many sites in striatum and olfactory tubercle and ³H]SPI twice as many sites in pituitary. 2) The kinetic was much shorter with ³H]RAC than ³H]SPI in striatum. 3) RAC, unlike SPI, did not exhibit limbic selectivity. 4) The modulation of ³H]RAC and ³H]SPI binding by endogenous DA were diametrically opposite: D-amphetamine decreased, and reserpine + α-methyl-p-tyrosine increased ³H]RAC binding in striatum whereas the opposite occured with ³H]SPI. This distinct binding pattern of ³H]RAC and ³H]SPI suggests that these two radioligands do not label the same receptor sites.