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

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.

Botulinum Neurotoxin-A Injected Intrastriatally into Hemiparkinsonian Rats Improves the Initiation Time for Left and Right Forelimbs in Both Forehand and Backhand Directions

“…One month after injection of 6-OHDA into the right MFB, the respective values were: left paw forehand: 3.958 ± 0.136, left paw backhand: 6.813 ± 0.136, right paw forehand: 10.993 ± 0.160, right paw backhand: 12.153 ± 0.175 ( Figure 3 B and Figure 5 B). Neither the first nor the second BoNT-A injection into the CPu significantly changed the number of AS made by either forepaw in either direction [ 58 ].…”

“…Comparing the ITs of movements of left and right forepaws both in forehand and backhand directions and apomorphine-induced rotations in individual rats 1 month after induction of hemi-PD revealed that these parameters are not significantly correlated ( Figure 5 A). Rotational behavior covered a wide range of values (−0.775 to +12.022 rpm; [ 58 ]). However, ITs were found rather constant (left paw: 2.600–4.827 s, right paw 0.424–0.813 s).…”

“…Comparing the AS of left and right paws both in the forehand and backhand directions with the number of the respective rotations 1 month after 6-OHDA injection showed that AS and rotations are not significantly correlated ( Figure 5 B). Values of AS of the left forepaw in hemi-PD rats ranged between 3.167 and 8.167 (left paw forehand: 3.958 ± 0.136, left paw backhand: 6.754 ± 0.163; [ 58 ]). Also, the AS of forelimb movements is a parameter independent of the degree of the respective apomorphine-induced rotations ( Figure 5 B).…”

“…Testing for correlations between ITs of left forepaws both in forehand and backhand directions and apomorphine-induced rotations in hemi-PD rats treated with BoNT-A or sham BoNT-A with various post injection survival times revealed no significant correlative dependency of both parameters at any time point ( Figure 6 A–F). Although BoNT-A both reduced ITs and rotational behavior in hemi-PD rats dependent on post BoNT-A injection survival time [ 58 ], seemingly both parameters are differently and independently influenced by intrastriatal BoNT-A.…”

“…Concerning the time-dependent outcome of BoNT-A application, these findings correspond to our prior results in an apomorphine-induced rotation test: injection of BoNT-A into the CPu of hemi-PD rats reduced apomorphine-induced rotation behavior significantly for at least 3 months [ 38 , 39 , 40 , 42 , 43 , 44 , 87 ]. In addition, compared with sham injections, a second BoNT-A again significantly decreased apomorphine-induced rotations, whereas the beneficial effect faded with longer post-injection survival times [ 58 ].…”