Dopamine receptor density measured by C-11 raclopride and NMSP in the same schizophrenic patients and normal subjects

Dopamine D2 receptor dimers in human and rat brain

“…The problem is further compounded when the receptor is measured in disease. For example, the density of brain dopamine D2 receptors in healthy volunteers is 15–16.7 pmol/ml when measured with [ 11 C]methylspiperone [1, 2], but, even in the same laboratory [3], is 25 pmol/ml when measured with [ 11 C]raclopride. Farde et al have also found a difference in these radioligand densities in healthy subjects [4, 5]and in schizophrenia patients [5, 6].…”

Discussion

“…These data indicate that the spiperone and benzamide congeners labeled different populations of the D 2 receptor, resolving the density discrepancies found with these two radioligands in human brain positron tomography Wong et al 1993;Nordstrom et al 1995;Farde et al 1990Farde et al , 1995Wong et al 1995). In other words, because the benzamide attaches to both monomers and dimers, the density of […”

“…11 C]-spiperone ranges from 15 to 24 pmol/ g Wong et al 1993;Nordstrom et al 1995), whereas the density of 0 2 sites labeled by [1 1 C]-raclopride ranges from 24 to 28 pmol/ g (Farde et al 1990(Farde et al , 1995Wong et al 1995 The balance between D 2 monomers and dimers may well depend on experimental conditions, as outlined for muscarinic receptor oligomers by Wreggett and Wells (1995), and this factor may account for identical 0 2 densities measured by Malmberg et al (1996).…”

“…11 C]-raclopride is invariably 20%1 higher (L. Farde, personal communication) or 80% higher (Wong et al 1992 than the density of […”

Discussion

“…It has been suggested that the former two bind more specifically to monomers than to dimers than does raclopride. Wong et al (1992) (Wong in preparation). This is consistent with review of other work that has demonstrated receptor elevations with NMSP but not raclopride using both in vivo PET and in vitro postmortem studies .…”