Comparison of Actions between L-DOPA and Different Dopamine Agonists in Striatal DA-Depleted Microcircuits In Vitro: Pre-Clinical Insights.

Comparison of Actions between L-DOPA and Different Dopamine Agonists in Striatal DA-Depleted Microcircuits In Vitro: Pre-Clinical Insights.

Publication date: May 09, 2019

Parkinson’s disease (PD) is a neurodegenerative illness presenting motor and non-motor symptoms due to the loss of dopaminergic terminals in basal ganglia, most importantly, the striatum. L-DOPA relieves many motor signs. Unfortunately, in the long term, L-DOPA use causes motor disabilities by itself and does not act in comorbid conditions such as depression. These deficiencies have led to search for drugs such as dopamine (DA) receptor agonists (DA-agonists) that allow the reduction of L-DOPA dose. Previously, we have identified the attributes of non-stimulated (resting) and cortical stimulated (active) striatal microcircuits following the activity of dozens of neurons simultaneously using calcium imaging in brain slices. We also have characterized the changes that take place in DA-depleted microcircuits in vitro. In control conditions, there is low spontaneous activity. After cortical stimulation (CtxS) sequences and alternation of neuronal ensembles activity occur, including reverberations. In contrast, DA-deprived circuits exhibit high spontaneous activity at rest, and a highly recurrent ensemble curtails alternation. Interestingly, CtxS briefly relieves these Parkinsonian signs in DA-depleted tissue. Here we compare the actions of some DA-agonists used in PD therapeutics on the pathological dynamics of DA-depleted microcircuits at rest and with CtxS; taking L-DOPA as reference. D-class agonists better reduce the excessive spontaneous activity of DA-depleted microcircuits. All DA-agonists tend to maintain ensemble alternation seen in control circuits after CtxS. However, quantitative analyses suggest differences in their actions: in general, DA-agonists only approximate L-DOPA actions. Nonetheless no treatment, including L-DOPA, completely restores microcircuit dynamics to control conditions.

Lara-Gonz’alez, E., Duhne, M., ‘Avila-Cascajares, F., Cruz, S., and Bargas, J. Comparison of Actions between L-DOPA and Different Dopamine Agonists in Striatal DA-Depleted Microcircuits In Vitro: Pre-Clinical Insights. 20747. 2019 Neuroscience.

Concepts Keywords
Basal Ganglia Neuroscience
Comorbid Levodopa-induced dyskinesia
Cortical Neuron
D Class Tyrosine hydroxylase
DA Parkinson’s disease
Depression Catecholamines
DOPA Organ systems
Dopamine Dopamine
Dopaminergic Branches of biology
Microcircuit Drugs
Neurodegenerative PD neurodegenerative illness
Neurons
Parkinson
Parkinsonian
Receptor
Spontaneous Activity
Striatal
Striatum

Semantics

Type Source Name
drug DRUGBANK Tropicamide
gene UNIPROT REST
drug DRUGBANK Calcium
gene UNIPROT SMIM10L2A
gene UNIPROT SMIM10L2B
disease MESH depression
drug DRUGBANK Dopamine
drug DRUGBANK Levodopa

Original Article

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