Autoradiographic distribution of the D1 agonist [3H]SKF 38393, in the rat brain and spinal cord. Comparison with the distribution of D2 dopamine receptors

Abstract

The regional distribution of the specific D1 agonist [3H]SKF 38393 (SKF 38393, 2,3,4,5-tetra-hydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) has been studied autoradiographically in the rat CNS. The binding of [3H]SKF 38393 to striatal sections was saturable, stereospecific, reversible, of high affinity (Kd = 9.9 nM) and partly sodium sensitive; it occurred at a single population of sites and possessed the pharmacological characteristics of the dopamine D1 receptor. The highest levels of [3H]SKF 38393 binding sites were found in the caudate-putamen, nucleus accumbens, olfactory tubercle and substantia nigra. Moderately high concentrations of the [3H]ligand were observed in the amygdala, endopyriform nucleus, nucleus olfactorius anterior, lateral septum, primary olfactory cortex, cerebellum (molecular layer) and spinal cord. An intermediate labelling was found in the thalamus, habenula, subthalamic nucleus, hypothalamus, ventral tegmental area, superior colliculus, hippocampus and cerebral cortex. Moderate levels of [3H]SKF 38393 binding were observed in the globus pallidus and arcuate nucleus. The autoradiographic distribution of [3H]SKF 38393 overlapped with that of [3H]N,n-propylnorapomorphine, a radioligand which labels the D2 dopamine receptors, in a number of dopamine-rich brain areas but there were several areas which exhibited a high density of [3H]SKF 38393 binding sites but undetectable concentrations of [3H]N,n-propylnorapomorphine. Moreover, in the spinal cord, the subregional localization of these [3H]ligands clearly differed. Intrastriatal injection of ibotenic acid caused a large decrease in [3H]SKF 38393 and [3H]N,n-propylnorapomorphine binding in the striatum and provoked a reduction of [3H]SKF 38393 but not [3H]N,n-propylnorapomorphine binding in the substantia nigra confirming the view that nigral D1 but not D2 receptors are located on striatonigral fibres.