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Abstract
Parkinson’s patients often suffer from depression and anxiety, for which there are no optimal treatments. Hemiparkinsonian (hemi-PD) rats were used to test whether intrastriatal Botulinum neurotoxin-A (BoNT-A) application could also have antidepressant-like properties in addition to the known improvement of motor performance. To quantify depression- and anxiety-like behavior, the forced swim test, tail suspension test, open field test, and elevated plus maze test were applied to hemi-PD rats injected with BoNT-A or vehicle. Furthermore, we correlated the results in the forced swim test, open field test, and elevated plus maze test with the rotational behavior induced by apomorphine and amphetamine. Hemi-PD rats did not show significant anxiety-like behavior as compared with Sham 6-OHDA- + Sham BoNT-A-injected as well as with non-injected rats. However, hemi-PD rats demonstrated increased depression-like behaviors compared with Sham- or non-injected rats; this was seen by increased struggling frequency and increased immobility frequency. Hemi-PD rats intrastriatally injected with BoNT-A exhibited reduced depression-like behavior compared with the respective vehicle-receiving hemi-PD animals. The significant effects of intrastriatally applied BoNT-A seen in the forced swim test are reminiscent of those found after various antidepressant drug therapies. Our data correspond with the efficacy of BoNT-A treatment of glabellar frown lines in treating patients with major depression and suggest that also intrastriatal injected BoNT-A may have some antidepressant-like effect on hemi-PD.
Highlights
In the present study, we aimed to examine a possible therapeutic effect of intrastriatal injections of Botulinum neurotoxin-A (BoNT-A) on depression-like behavior in the hemi-Parkinson’s disease (PD) rat model induced by medial forebrain bundle (MFB) lesion, using the forced swim test and tail suspension test, and on anxietylike behavior as well as a motor activity using the open field test and elevated plus maze test
In hemi-PD rats, intrastriatally applied botulinum neurotoxin-A (BoNT)-A has a positive effect on motor dysfunction without impairing cognitive and peripheral cholinergic functions [109,110,111,112,113,114,115,116,117,118,119,120]
The effects of BoNT-A injected into the dopamine-depleted CPu are reminiscent of the actions of several antidepressant agents [365,366]
Summary
Parkinson’s disease (PD) is the most common and complex age-related chronic neurodegenerative movement disorder [1,2,3,4], hallmarked by the progressive loss of about. Non-motor symptoms are increasingly recognized as relevant in the disease-state, given the associated alterations in mood (depression and anxiety) and cognition [12,13,14]. Throughout PD progression, motor impairments are generally preceded by non-motor symptoms such as depression, anxiety, olfactory deficit, sleep behavior disorder, and constipation, sometimes by up to ten years [13,15,16,17,18,19,20]. Non-motor symptoms of PD are very often overlooked though they are increasingly being investigated and have a very crucial impact on the clinical care and patient’s quality of life [10,20,21,22,23,24]
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