Effect of selective and non-selective serotonin receptor activation on l-DOPA-induced therapeutic efficacy and dyskinesia in parkinsonian rats

Tronci, Elisabetta; Fidalgo, Camino; Stancampiano, Roberto; Carta, Manolo

doi:10.1016/j.bbr.2015.06.034

Cited by 20 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In hemi-PD rats our results confirmed those of many others (Schallert et al, 1992; Mukhida et al, 2001; Kelsey et al, 2004; Tseng et al, 2005; Manfredsson et al, 2007; Pioli et al, 2008; Fang et al, 2010; Seeger-Armbruster and von Ameln-Mayerhofer, 2013; Shin et al, 2014; Tronci et al, 2015) showing the severe impairment of the contralateral paw in combination with unaltered stepping performance of the ipsilateral paw (Winkler et al, 1996; Kelsey et al, 2004; Pinna et al, 2010). The motor initiation deficits in the forelimbs, analogous to limb akinesia and gait problems in PD patients, were produced by DA depletion (Sabol et al, 1985; Fairley and Marshall, 1986; Salamone et al, 1993).…”

Section: Discussionsupporting

confidence: 89%

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Antipova

Holzmann

Schmitt

et al. 2017

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. The loss of dopaminergic neurons in the substantia nigra leads to a disinhibition of cholinergic interneurons in the striatum. Pharmacotherapeutical strategies of PD-related hypercholinism have numerous adverse side effects. We previously showed that ipsilateral intrastriatal injections of 1 ng in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats inhibit apomorphine-induced rotation behavior significantly up to 6 months. In this study, we extended the behavioral testing of ipsilateral botulinum neurotoxin A (BoNT-A)-injection and additionally investigated the impact of intrastriatal BoNT-A-injections contralateral to the 6-OHDA-lesioned hemisphere on the basal ganglia circuity and motor functions. We hypothesized that the interhemispheric differences of acetylcholine (ACh) concentration seen in unilateral hemi-PD should be differentially and temporally influenced by the ipsilateral or contralateral injection of BoNT-A. Hemi-PD rats were injected with 1 ng BoNT-A or vehicle substance into either the ipsilateral or contralateral striatum 6 weeks after 6-OHDA-lesion and various behaviors were tested. In hemi-PD rats intrastriatal ipsilateral BoNT-A-injections significantly reduced apomorphine-induced rotations and increased amphetamine-induced rotations, but showed no significant improvement of forelimb usage and akinesia, lateralized sensorimotor integration and also no effect on spontaneous locomotor activity. However, intrastriatal BoNT-A-injections contralateral to the lesion led to a significant increase of the apomorphine-induced turning rate only 2 weeks after the treatment. The apomorphine-induced rotation rate decreases thereafter to a value below the initial rotation rate. Amphetamine-induced rotations were not significantly changed after BoNT-A-application in comparison to sham-treated animals. Forelimb usage was temporally improved by contralateral BoNT-A-injection at 2 weeks after BoNT-A. Akinesia and lateralized sensorimotor integration were also improved, but contralateral BoNT-A-injection had no significant effect on spontaneous locomotor activity. These long-ranging and different effects suggest that intrastriatally applied BoNT-A acts not only as an inhibitor of ACh release but also has long-lasting impact on transmitter expression and thereby on the basal ganglia circuitry. Evaluation of changes of transmitter receptors is subject of ongoing studies of our group.

show abstract

Section: Discussionsupporting

confidence: 89%

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Antipova

Holzmann

Schmitt

et al. 2017

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In both rodent and monkey models, it abolished LD-mediated motor improvements, suggesting that it may have a narrow therapeutic window [93]. However, the loss of LD efficacy proved to be mitigated by co-administration with 5-hydroxy-tryptophan [95]. When tested in a clinical Phase I/IIa study, Eltoprazine attenuated LID without affecting the antiparkinsonian action of LD [96].…”

Section: Serotonin Receptorsmentioning

confidence: 99%

Receptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson’s Disease

et al. 2019

View full text Add to dashboard Cite

Levodopa (LD) is the most effective drug in the treatment of Parkinson’s disease (PD). However, although it represents the “gold standard” of PD therapy, LD can cause side effects, including gastrointestinal and cardiovascular symptoms as well as transient elevated liver enzyme levels. Moreover, LD therapy leads to LD-induced dyskinesia (LID), a disabling motor complication that represents a major challenge for the clinical neurologist. Due to the many limitations associated with LD therapeutic use, other dopaminergic and non-dopaminergic drugs are being developed to optimize the treatment response. This review focuses on recent investigations about non-dopaminergic central nervous system (CNS) receptor ligands that have been identified to have therapeutic potential for the treatment of motor and non-motor symptoms of PD. In a different way, such agents may contribute to extending LD response and/or ameliorate LD-induced side effects.

show abstract

“…[121122] Eltoprazine (5 mg/d) showed antidyskinetic effects without reducing normal motor responses to levodopa,[47] through the restoration of LTP and synaptic depotentiation in a subset of striatal spiny projection neurons. [123] However, in another rat model study, reduced levodopa-induced mobility was observed despite the antidyskinesia properties of eltoprazine.…”

Section: Serotonergic Agentsmentioning

confidence: 99%

“…[123] However, in another rat model study, reduced levodopa-induced mobility was observed despite the antidyskinesia properties of eltoprazine. [122] A combination of eltoprazine and preladenant reduced dyskinesia and maintained the full therapeutic effects of a low dose of levodopa. [124] A Phase II study is currently active.…”

Section: Serotonergic Agentsmentioning

confidence: 99%

Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson's Disease

Chen

2017

Chinese Medical Journal

View full text Add to dashboard Cite

Objective:The aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson's disease (PD).Data Sources:Papers in English published in PubMed, Cochrane, and Ovid Nursing databases between January 1988 and November 2016 were searched using the following keywords: PD, nondopaminergic therapy, adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator. We also reviewed the ongoing clinical trials in the website of clinicaltrials.gov.Study Selection:Articles related to the nondopaminergic treatment of motor symptoms in PD were selected for this review.Results:PD is conventionally treated with dopamine replacement strategies, which are effective in the early stages of PD. Long-term use of levodopa could result in motor complications. Recent studies revealed that nondopaminergic systems such as adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator pathways could include potential therapeutic targets for motor symptoms, including motor fluctuations, levodopa-induced dyskinesia, and gait disorders. Some nondopaminergic drugs, such as istradefylline and amantadine, are currently used clinically, while most such drugs are in preclinical testing stages. Transitioning of these agents into clinically beneficial strategies requires reliable evaluation since several agents have failed to show consistent results despite positive findings at the preclinical level.Conclusions:Targeting nondopaminergic transmission could improve some motor symptoms in PD, especially the discomfort of dyskinesia. Although nondopaminergic treatments show great potential in PD treatment as an adjunct therapy to levodopa, further investigation is required to ensure their success.

show abstract

Effect of selective and non-selective serotonin receptor activation on l-DOPA-induced therapeutic efficacy and dyskinesia in parkinsonian rats

Cited by 20 publications

References 24 publications

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Receptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson’s Disease

Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson's Disease

Contact Info

Product

Resources

About