Abstract
Here we analyzed the mechanisms of mutual influence of serotonin, dopamine, and acetylcholine on the activity of neurons of the dorsal striatum and motor activity. We used the data that show that 5-HT1B, D1, and M4 receptors of these neuromodulators are predominantly located on the striatonigral neurons and 5-HT2A, D2, and M1 receptors are located on the striatopallidal neurons, which give rise, respectively, to the direct and indirect pathways via the basal ganglia. Cholinergic interneurons of the striatum have 5-HT1A, 5-HT2C, 5-HT7, and D2 receptors and serotonergic terminals have 5-HT1A auto-receptors. On the basis of the types of G-proteins that are coupled to the mentioned receptors and our previously proposed modulation rules for strong corticostriatal inputs, we proposed a hypothetical mechanism of mutual influence of neuromodulators on the functioning of neuronal network: motor cortex-basal ganglia-thalamus-motor cortex. According to this mechanism, enhancement of the action on dopamine receptors, as well as a decrease in the action on serotonin and muscarinic receptors on spiny neurons of the dorsal (motor) striatum, must synergistically promote enhancement of locomotor activity due to an increase in disinhibition of thalamic cells via direct pathway through the basal ganglia and a decrease in their inhibition via an indirect pathway through the basal ganglia. According to the proposed mechanism, enhancement of the motor activity during Parkinson’s disease, as well as weakening of catalepsy induced by typical antipsychotic drugs (antagonists of D2 receptors), may be caused by antagonists of 5-HT1B, 5-HT2A, 5-HT2C, and 5-HT7 receptors. For weakening of dyskinesia induced by levodopa during treatment of Parkinson’s disease, it may be worth-while to use agonists of 5-HT1B and 5-HT2A receptors. The use of agonists of 5-HT1A receptors for weakening of levodopa-induced dyskinesia should be combined with antagonists of 5-HT2C receptors to prevent aggravation of the symptoms of Parkinson’s disease. The proposed mechanism allows one to explain the contradictory data of the effect of serotonin via different types of receptors on both weakening of dyskinesia and enhancement of motor activity. The consequences of the proposed mechanism are in agreement with the known results of experimental studies and may be useful for the development of new drugs for the treatment of Parkinson’s disease and novel atypical antipsychotic drugs.
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Abbreviations
- BG:
-
basal ganglia
- PD:
-
Parkinson’s disease
- GPe and GPi:
-
external and internal parts of the globus pallidus
- LTD:
-
long-term depression
- LID:
-
levodopa-induced dyskinesia
- LTP:
-
long-term potentiation
- MC-BG-Th-MC:
-
neuronal network motor cortex-basal ganglia-thalamus-motor cortex
- SNpc and SNpr:
-
substantia nigra pars compacta and pars reticulata
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Original Russian Text © I.G. Silkis, 2014, published in Neirokhimiya, 2014, Vol. 31, No. 3, pp. 185–199.
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Silkis, I.G. Mutual influence of serotonin and dopamine on the functioning of the dorsal striatum and motor activity (hypothetical mechanism). Neurochem. J. 8, 149–161 (2014). https://doi.org/10.1134/S1819712414030118
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DOI: https://doi.org/10.1134/S1819712414030118