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Intrastriatal administration of botulinum neurotoxin A normalizes striatal D 2 R binding and reduces striatal D 1 R binding in male hemiparkinsonian rats
Author(s) -
Wedekind Franziska,
Oskamp Angela,
Lang Markus,
Hawlitschka Alexander,
Zilles Karl,
Wree Andreas,
Bauer Andreas
Publication year - 2018
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24110
Subject(s) - apomorphine , dopaminergic , striatum , oxidopamine , basal ganglia , forelimb , raclopride , medicine , neurotoxin , endocrinology , dopamine , nigrostriatal pathway , chemistry , neuroscience , psychology , substantia nigra , central nervous system
Cerebral administration of botulinum neurotoxin A (BoNT‐A) has been shown to improve disease‐specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT‐A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6‐hydroxydopamine (6‐OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT‐A, while the others received vehicle ( n = 7). All animals were tested for asymmetric motor behavior (apomorphine‐induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6‐OHDA lesion alone induced a unilateral PD‐like phenotype and a 13% increase of striatal D 2 R. BoNT‐A treatment reduced the asymmetry in both apomorphine‐induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT‐A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6‐OHDA rat model of PD.