Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum...

Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D₁, D₂/D₃, α₁, α₂, and 5HT_2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D₁ receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D₂/D₃ receptor density, and 50% reduction in 5HT_2A receptor density. α₁ receptor density remained unaltered in hemi-PD and α₂ receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D₂/D₃ receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D₂/D₃ receptor density.