Buspirone anti-dyskinetic effect is correlated with temporal normalization of dysregulated striatal DRD1 signalling in l-DOPA-treated rats

Azkona, Garikoitz; Sagarduy, Ainhoa; Aristieta, Asier; Vazquez, Nerea; Zubillaga, Verónica; Ruiz-Ortega, José Ángel; Pérez‐Navarro, Esther; Ugedo, Luisa; Sánchez‐Pernaute, Rosario

doi:10.1016/j.neuropharm.2013.11.024

Cited by 26 publications

(18 citation statements)

References 65 publications

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“…in combination with the peripheral decarboxylase inhibitor benserazide (12 mg·kg −1 , i.p.) over 3 weeks (Aristieta et al, 2016; Aristieta, Ruiz‐Ortega, Morera‐Herreras, Miguelez, & Ugedo, 2019; Azkona et al, 2014; Dekundy, Lundblad, Danysz, & Cenci, 2007). Abnormal involuntary movements were scored according to the scale described by Cenci and Lundblad (2007).…”

Section: Methodsmentioning

confidence: 99%

“…In this regard, we have observed that buspirone, a 5‐HT 1A receptor partial agonist, inhibits neuronal activity in the subthalamic nucleus in control rats but has no effect after DA depletion (Sagarduy et al, 2016). Another study found that it efficiently improves the behavioural score and reduces certain molecular changes associated with l ‐DOPA‐induced dyskinesia (Azkona et al, 2014). In addition, DA depletion and/or chronic administration of l ‐DOPA have been associated with dysfunctional neuronal activity in several brain structures among which is the substantia nigra reticulata (SNr) (Aristieta, Ruiz‐Ortega, Miguelez, Morera‐Herreras, & Ugedo, 2016; Tseng, Riquelme, Belforte, Pazo, & Murer, 2000).…”

Section: Introductionmentioning

confidence: 99%

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6‐Hydroxydopamine lesion and levodopa treatment modify the effect of buspirone in the substantia nigra pars reticulata

Vegas-Suárez

Pisanò

Requejo

et al. 2020

British J Pharmacology

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Background and Purpose l‐DOPA‐induced dyskinesia (LID) is considered a major complication in the treatment of Parkinson's disease (PD). Buspirone (5‐HT1A partial agonist) have shown promising results in the treatment of PD and LID, however no 5‐HT‐based treatment has been approved in PD. The present study was aimed to investigate how the substantia nigra pars reticulata (SNr) is affected by buspirone and whether it is a good target to study 5‐HT antidyskinetic treatments. Experimental Approach Buspirone was studied using in vivo single‐unit, electrocorticogram, local field potential recordings along with microdialysis and immunohistochemistry in naïve/sham, 6‐hydroxydopamine (6‐OHDA)‐lesioned or 6‐OHDA‐lesioned and l‐DOPA‐treated (6‐OHDA/l‐DOPA) rats. Key Results Local buspirone inhibited SNr neuron activity in all groups. However, systemic buspirone reduced burst activity in 6‐OHDA‐lesioned rats (with or without l‐DOPA treatment), whereas 8‐OH‐DPAT, a full 5‐HT1A agonist induced larger inhibitory effects in sham animals. Neither buspirone nor 8‐OH‐DPAT markedly modified the low‐frequency oscillatory activity in the SNr or synchronization within the SNr with the cortex. In addition, local perfusion of buspirone increased GABA and glutamate release in the SNr of naïve and 6‐OHDA‐lesioned rats but no effect in 6‐OHDA/l‐DOPA rats. In the 6‐OHDA/l‐DOPA group, increased 5‐HT transporter and decreased 5‐HT1A receptor expression was found. Conclusions and Implications The effects of buspirone in SNr are influenced by dopamine loss and l‐DOPA treatment. The present results suggest that the regulation of burst activity of the SNr induced by DA loss may be a good target to test new drugs for the treatment of PD and LID.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

6‐Hydroxydopamine lesion and levodopa treatment modify the effect of buspirone in the substantia nigra pars reticulata

Vegas-Suárez

Pisanò

Requejo

et al. 2020

British J Pharmacology

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“…In these days, various approaches using 5-HT 1A agonists target mainly motor fluctuation in PD [138-142, 161-167] (Table 1). Eltoprazine, a selective 5-HT 1A and 5-HT 1B agonist, is currently being tested in clinical trials for motor complications derived from dopaminergic therapy in PD [140, 141].…”

Section: Serotonin 1a (5-ht1a) Receptors On Astrocytes As a Novel Tarmentioning

confidence: 99%

Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease

Miyazaki

Asanuma²

2016

CMC

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Astrocytes are the most abundant neuron-supporting glial cells in the central nervous system. The neuroprotective role of astrocytes has been demonstrated in various neurological disorders such as amyotrophic lateral sclerosis, spinal cord injury, stroke and Parkinson’s disease (PD). Astrocyte dysfunction or loss-of-astrocytes increases the susceptibility of neurons to cell death, while astrocyte transplantation in animal studies has therapeutic advantage. We reported recently that stimulation of serotonin 1A (5-HT1A) receptors on astrocytes promoted astrocyte proliferation and upregulated antioxidative molecules to act as a neuroprotectant in parkinsonian mice. PD is a progressive neurodegenerative disease with motor symptoms such as tremor, bradykinesia, rigidity and postural instability, that are based on selective loss of nigrostriatal dopaminergic neurons, and with non-motor symptoms such as orthostatic hypotension and constipation based on peripheral neurodegeneration. Although dopaminergic therapy for managing the motor disability associated with PD is being assessed at present, the main challenge remains the development of neuroprotective or disease-modifying treatments. Therefore, it is desirable to find treatments that can reduce the progression of dopaminergic cell death. In this article, we summarize first the neuroprotective properties of astrocytes targeting certain molecules related to PD. Next, we review neuroprotective effects induced by stimulation of 5-HT1A receptors on astrocytes. The review discusses new promising therapeutic strategies based on neuroprotection against oxidative stress and prevention of dopaminergic neurodegeneration.

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“…Cenci's protocol has become the most widely accepted option for evaluating dyskinesia in 6-OHDA-lesioned rodents. On the basis of this protocol, numerous pharmacological trials have led to the discoveries of several promising therapeutic targets in recent years, including the GABA system (77–79), the serotonin system (80–84), adenosine receptors (85–88), opioid receptors (89–92), neuronal nitric oxide synthase inhibition (93), β 2 nicotinic receptors (94–98), and cation channels (99, 100). Confidence in the application of rodent models has been further boosted by the findings that the GABA system and serotonin system translate quite well when these agents are applied in non-human primate models and clinical trials (8).…”

Section: Current Usage and Advances In The Use Of Rodents In Dyskinesmentioning

confidence: 99%

The Rodent Models of Dyskinesia and Their Behavioral Assessment

et al. 2019

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Dyskinesia, a major motor complication resulting from dopamine replacement treatment, manifests as involuntary hyperkinetic or dystonic movements. This condition poses a challenge to the treatment of Parkinson's disease. So far, several behavioral models based on rodent with dyskinesia have been established. These models have provided an important platform for evaluating the curative effect of drugs at the preclinical research level over the past two decades. However, there are differences in the modeling and behavioral testing procedures among various laboratories that adversely affect the rat and mouse models as credible experimental tools in this field. This article systematically reviews the history, the pros and cons, and the controversies surrounding rodent models of dyskinesia as well as their behavioral assessment protocols. A summary of factors that influence the behavioral assessment in the rodent dyskinesia models is also presented, including the degree of dopamine denervation, stereotaxic lesion sites, drug regimen, monitoring styles, priming effect, and individual and strain differences. Besides, recent breakthroughs like the genetic mouse models and the bilateral intoxication models for dyskinesia are also discussed.

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Buspirone anti-dyskinetic effect is correlated with temporal normalization of dysregulated striatal DRD1 signalling in l-DOPA-treated rats

Cited by 26 publications

References 65 publications

6‐Hydroxydopamine lesion and levodopa treatment modify the effect of buspirone in the substantia nigra pars reticulata

6‐Hydroxydopamine lesion and levodopa treatment modify the effect of buspirone in the substantia nigra pars reticulata

Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease

The Rodent Models of Dyskinesia and Their Behavioral Assessment

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