Topology of intrastriatal dopaminergic grafts determines functional and emotional outcome in neurotoxin-lesioned rats

Jungnickel, Julia; Kalve, Ieva; Reimers, Linda; Nobre, André; Wesemann, Maike; Ratzka, Andreas; Halfer, Nina; Lindemann, Christina; Schwabe, Kerstin; Töllner, Kathrin; Gernert, Manuela; Grothe, Claudia

doi:10.1016/j.bbr.2010.07.023

Cited by 27 publications

(8 citation statements)

References 41 publications

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“…Curiously, experimental data in animal models of PD is also inconclusive. While a recent study showed no effect of bilateral MFB lesions on anxiety [33], previous studies had reported a significant anxiolytic effect of bilateral 6-OHDA lesions in the striatum [34], or even higher levels of anxiety in animals with either unilateral MFB lesions [35,36] or bilateral striatal lesions [37]. Our results on the EPM show no signs for the presence of anxiety-like behavior in animals with both incomplete and complete lesions.…”

Section: Discussioncontrasting

confidence: 76%

Behavioral characterization of the 6-hydroxidopamine model of Parkinson’s disease and pharmacological rescuing of non-motor deficits

Carvalho

Campos

Coimbra

et al. 2013

Mol Neurodegeneration

149

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BackgroundParkinson’s disease (PD) is a chronic neurodegenerative condition that is characterized by motor symptoms as a result of dopaminergic degeneration, particularly in the mesostriatal pathway. However, in recent years, a greater number of clinical studies have focused on the emergence of non-motor symptoms in PD patients, as a consequence of damage on the mesolimbic and mesocortical dopaminergic networks, and on their significant impact on the quality of life of PD patients. Herein, we performed a thorough behavioral analysis including motor, emotional and cognitive dimensions, of the unilateral medial forebrain bundle (MFB) 6-hydroxidopamine (6-OHDA)-lesioned model of PD, and further addressed the impact of pharmacological interventions with levodopa and antidepressants on mood dimensions.ResultsBased on apomorphine-induced turning behaviour and degree of dopaminergic degeneration, animals submitted to MFB lesions were subdivided in complete and incomplete lesion groups. Importantly, this division also translated into a different severity of motor and exploratory impairments and depressive-like symptoms; in contrast, no deficits in anxiety-like and cognitive behaviors were found in MFB-lesioned animals. Subsequently, we found that the exploratory and the anhedonic behavioural alterations of MFB-lesioned rats can be partially improved with the administration of both levodopa or the antidepressant bupropion, but not paroxetine.ConclusionsOur results suggest that this model is a relevant tool to study the pathophysiology of motor and non-motor symptoms of PD. In addition, the present data shows that pharmacological interventions modulating dopaminergic transmission are also relevant to revert the non-motor behavioral deficits found in the disease.

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Section: Discussioncontrasting

confidence: 76%

Behavioral characterization of the 6-hydroxidopamine model of Parkinson’s disease and pharmacological rescuing of non-motor deficits

Carvalho

Campos

Coimbra

et al. 2013

Mol Neurodegeneration

149

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“…In previous experimental studies, the results of anxiety-like behavior in rat models of PD were inconsistent. In rats with unilateral MFB lesions, several studies found increased anxiety-like behaviors in the EPM, OFT, social interaction or acoustic startle response tests (Eskow Jaunarajs et al, 2010;Jungnickel et al, 2011), whereas some others indicated that there are no effects on anxiety-like behaviors (Carvalho et al, 2013;Delaville et al, 2012). The discrepancy could be also caused by the site of 6-OHDA injection, the extent of the lesion, unilateral or bilateral lesions, used anxiety paradigms and time frame for the behavior tests.…”

Section: Anxiety-like Behaviors Involve Increased Firing Activity Of mentioning

confidence: 91%

Activation of 5-HT1A receptors in the medial subdivision of the central nucleus of the amygdala produces anxiolytic effects in a rat model of Parkinson's disease

Sun

Wang

et al. 2015

Neuropharmacology

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“…Depression-like behaviors have been demonstrated in rats with 6-OHDA lesions; however, the respective results have been inconsistent among studies [ 60 , 74 , 169 , 179 , 180 , 181 , 182 , 184 , 185 , 186 ]. In hemi-PD rats with complete or nearly complete unilateral 6-OHDA lesions of the MFB, several studies found increased immobility time in the forced swim test (FST) and decreased sucrose consumption, respectively [ 74 , 169 , 172 ].…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, the results of anxiety-like behaviors in different 6-OHDA rat models of PD are also inconsistent [ 172 ]. In rats with unilateral MFB lesions, several studies found that these rats showed increased anxiety-like behaviors in the elevated plus maze test (EPM), locomotor chamber, or social interaction tests [ 182 , 186 ]. Other studies using the same model, however, showed no effects on anxiety-like behaviors in the EPM, open field test (OFT), or acoustic startle response test [ 169 , 184 , 187 ].…”

Section: Introductionmentioning

confidence: 99%

Antidepressant-Like Properties of Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease

Antipova

Holzmann

Hawlitschka

et al. 2021

Toxins

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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.

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Topology of intrastriatal dopaminergic grafts determines functional and emotional outcome in neurotoxin-lesioned rats

Cited by 27 publications

References 41 publications

Behavioral characterization of the 6-hydroxidopamine model of Parkinson’s disease and pharmacological rescuing of non-motor deficits

Behavioral characterization of the 6-hydroxidopamine model of Parkinson’s disease and pharmacological rescuing of non-motor deficits

Activation of 5-HT1A receptors in the medial subdivision of the central nucleus of the amygdala produces anxiolytic effects in a rat model of Parkinson's disease

Antidepressant-Like Properties of Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease

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