Evidence for a functional role of the dopamine D3 receptors in the cerebellum.

Abstract

It has recently been shown that the lobules 9 and 10 of the cerebellum contain high densities of dopamine D3 receptors (and almost no D2 receptors [Bouthenet, M.L., Souil, E., Martres, M.P., Sokoloff, P., Giros, B. and Schwartz, J.C., Brain Res., 564 (1991) 203-219; Sokoloff, P., Giros, B., Martres, M.P., Bouthenet, M.L. and Schwartz, J.C., Nature, 347 (1990) 146-151]), and the functional role of this cerebellar dopamine system is unknown. In this study, using microinjections of dopamine receptor ligands into the lobules 9 and 10 of the cerebellum and into the nucleus accumbens, we show that the cerebellar dopamine D3 receptors have a functional role in the regulation of locomotor activity. When microinjected into the lobules 9 and 10 of the cerebellum, amisulpride (a dopamine D2 and D3 antagonist) and nafadotride (a preferential D3 antagonist) dose-dependently alter locomotor activity. At low doses, both agents stimulate locomotor activity, while inhibition is observed at higher doses. Haloperidol (a D2 antagonist) and apomorphine (a dopamine agonist) have no effects at low doses, but decrease locomotor activity at high doses. Similar effects are found in the nucleus accumbens, however the effects are stronger in the nucleus accumbens than in the cerebellum. Therefore, the dopamine D3 receptor system in lobules 9 and 10 of the cerebellum has a functional role, similar but weaker than the D3 receptor system in the nucleus accumbens.