Differential labelling of dopamine receptors in rat brain in vivo: Comparison of [ 3H]piribedil, [ 3H]S 3608 and [ 3H]N,n-propylnorapomorphine

Abstract

The in vivo distribution of radioactivity in brain and labelling of cerebral dopamine receptors in rats derived from the administration of the atypical dopamine agonists [ 3H]piribedil and [ 3H]S 3608 has been compared to that of the classical dopamine agonist [ 3H]N,n-propylnorapomorphine (NPA). Radioactivity derived from [ 3H]piribedil accumulated in the substantia nigra, nucleus accumbens and cervical spinal cord, and this accumulation was prevented by administration of (+)-butaclamol and apomorphine only in substantia nigra and the nucleus accumbens. Radioactivity derived from [ 3H]S 3608 accumulated in the same areas and, additionally, in the frontal cortex and tuberculum olfactorium; this accumulation was prevented by administration of (+)-butaclamol and apomorphine only in substantia nigra, nucleus accumbens and tuberculum olfactorium. Neither ligand caused accumulation of radioactivity in the striatum. In contrast, radioactivity derived from [ 3H]NPA accumulated in the substantia nigra, nucleus accumbens, striatum, and tuberculum olfactorium. Radioactivity derived from [ 3H]NPA was prevented from accumulating in all these areas by (+)-butaclamol and by apomorphine, but piribedil only prevented accumulation in the substantia nigra and nucleus accumbens and S 3608 only prevented accumulation in substantia nigra, tuberculum olfactorium and nucleus accumbens. Neither piribedil nor S 3608 prevented accumulation of radioactivity derived from [ 3H]NPA in the striatum. Piribedil and S 3608 showed equal capacity in vitro to displace [ 3H]spiperone and [ 3H]NPA from striatal or nucleus accumbens tissue preparations. These results suggest that, in vivo piribedil and S 3608 selectively interact with dopamine receptors in the substantia nigra and nucleus accumbens, but not with those in striatum, perhaps due to differential distribution within brain.