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Toxins 2018, 10(9), 368; https://doi.org/10.3390/toxins10090368

Repeated Intrastriatal Botulinum Neurotoxin-A Injection in Hemiparkinsonian Rats Increased the Beneficial Effect on Rotational Behavior

1
Institute of Anatomy, Rostock University Medical Center, D-18057 Rostock, Germany
2
Institute of Medical Genetics, Rostock University Medical Center, D-18057 Rostock, Germany
3
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Macroscopic and Clinical Anatomy, Medical University of Graz, A-8010 Graz, Austria
*
Author to whom correspondence should be addressed.
Received: 22 August 2018 / Revised: 4 September 2018 / Accepted: 8 September 2018 / Published: 11 September 2018
(This article belongs to the Special Issue Botulinum Toxin Treatment of Movement Disorders)
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Abstract

Injection of botulinum neurotoxin-A (BoNT-A) into the striatum of hemiparkinsonian (hemi-PD) rats reduced apomorphine-induced rotation behavior significantly, for at least 3 months. Thereafter, rotation behavior increased again. We injected hemi-PD rats with 1 ng BoNT-A twice, the second injection following 6 months after the first one and tested the rats for apomorphine-induced rotations and spontaneous motor behaviors, i.e., corridor task and stepping test. To test the hypothesis that BoNT-A reduced striatal hypercholinism in hemi-PD rats, the acetylcholinesterase inhibitor donepezil was injected prior to separate apomorphine-induced rotation tests. In hemi-PD rats, the first BoNT-A injection led to a clear reduction of the apomorphine-induced rotations, and the second BoNT-A injection to a more massive and prolonged reaction. In hemi-PD rats whose apomorphine-induced rotation behavior was strongly reduced by an intrastriatal BoNT-A, subsequent donepezil injections led to significant increases of the rotation rate. Concerning corridor task and stepping test, neither first nor second BoNT-A injections changed hemi-PD rats’ behavior significantly. The data give evidence for the possibility of repeated intrastriatal administrations of BoNT-A, for treatment of motor symptoms in experimental hemi-PD over a longer time. View Full-Text
Keywords: botulinum neurotoxin-A; striatum; basal ganglia; donepezil; acetylcholine; 6-OHDA botulinum neurotoxin-A; striatum; basal ganglia; donepezil; acetylcholine; 6-OHDA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Hawlitschka, A.; Holzmann, C.; Wree, A.; Antipova, V. Repeated Intrastriatal Botulinum Neurotoxin-A Injection in Hemiparkinsonian Rats Increased the Beneficial Effect on Rotational Behavior. Toxins 2018, 10, 368.

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