Regulation of dopamine D3 receptor in the striatal regions and substantia nigra in diffuse Lewy body disease

- Quantitative autoradiography of dopamine D1, D2, D3 receptors, VMAT2 and DAT.
- Dopamine D2 and D3 receptor densities were measured using a novel procedure.
- In Lewy body disease, D3 receptors were upregulated in the striatum.

The regulation of D3 receptor has not been well documented in diffuse Lewy body disease (DLBD). In this study, a novel D3-preferring radioligand [3H]WC-10 and a D2-preferring radioligand [3H]raclopride were used and the absolute densities of the dopamine D3 and D2 receptors were determined in the striatal regions and substantia nigra (SN) from postmortem brains from five cases of DLBD, which included dementia with Lewy bodies (DLB, n = 4) and Parkinson disease dementia (PDD, n = 1). The densities of the dopamine D1 receptor, vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT) were also measured by quantitative autoradiography using [3H]SCH23390, [3H]dihydrotetrabenazine, and [3H]WIN35428, respectively. The densities of these dopaminergic markers were also measured in the same brain regions in 10 age-matched control cases. Dopamine D3 receptor density was significantly increased in the striatal regions including caudate, putamen and nucleus accumbens (NAc). There were no significant changes in the dopamine D1 and D2 receptor densities in any brain regions measured. VMAT2 and DAT densities were reduced in all the brain regions measured in DLB/PDD, however, the significant reduction was found in the putamen for DAT and in the NAc and SN for VMAT2. The decrease of dopamine pre-synaptic markers implies neuronal loss in the substantia nigra pars compacta (SNpc) in these DLB/PDD cases, while the increase of D3 receptors in striatal regions could be attributed to dopaminergic medication history and psychiatric states such as hallucinations. Whether it also reflects compensatory regulation upon dopaminergic denervation warrants further confirmations on larger populations.