CHARACTERIZATION OF BINDING-SITES FOR [I-125] R(+)TRANS-7-OH-PIPAT IN RAT-BRAIN

Binding characteristics of a novel radioiodinated ligand, [I-125]R(+)trans-7-hydroxy-2-(N-n-propyl-N-3'-iodo-2'-propenyl) aminotetralin ([I-125]R(+)trans-7-OH-PIPAT), were evaluated using homogenate binding and autoradiographic techniques in rat brain. [I-125]R(+)trans-7-OH-PIPAT bound to sites (dopamine receptors) in homogenates of rat basal forebrain (including caudate putamen, nucleus accumbens and olfactory tubercle) with a high affinity (K-d = 0.42 nM). A majority (70%) of the sites labeled by [I-125]R(+)trans-7-OH-PIPAT in basal forebrain were GTP-sensitive. In rat hippocampal homogenates, specific and saturable binding of [I-125]R(+)trans-7-OH-PIPAT to 5-HT1A receptors, with a K-d value of 1.4nM and a B-max value of 210 fmol/mg protein, was observed. Binding of [I-125]R(+)trans-7-OH-PIPAT to sigma sites was also demonstrated in rat cerebellar homogenates. In the presence of GTP (to inhibit binding to D2 and 5-HT1A receptors) and DTG (to inhibit binding to sigma sites), dopamine D3 receptors could be selectively labeled with [I-125]R(+)trans-7-OH-PIPAT. [I-125]R(+)trans-7-OH-PIPAT offers several unique advantages, including high specific activity and high affinity binding, which make it an excellent probe for the investigation and characterization of the distribution of dopamine D3 receptors.