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Distinct binding patterns of [3H]raclopride and [3H]spiperone at dopamine D2 receptors in vivo in rat brain. Implications for pet studies.

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 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 + alpha-methyl-p-tyrosine increased [3H]RAC binding in striatum whereas the opposite occurred 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.