ROLE OF 5-HT2C RECEPTORS IN DYSKINESIA
Keywords:
Tardive dyskinesia, Extrapyramidal system, Medium spiny neurons, 5-HT2C receptors, Inverse agonismAbstract
By integrating knowledge gained by pharmacogenetic, neuroanatomical and pharmacological studies, a model can be constructed how serotonin (5-HT) affects the vulnerability to induce tardive dyskinesia. From neuroanatomical studies, it can be concluded that 5-HT inhibits the release of dopamine (DA) within the dorsal striatum by affecting 5-HT2C receptors and also within the ventral striatum and prefrontal cortex by affecting 5-HT2A receptors. However, considering the low affinity of DA for its receptors, it is unlikely that the so released DA is able to displace atypical antipsychotics from DA D2 and D3 receptors. 5-HT2C receptors and, to a lesser extent, 5-HT2A receptors, have constitutive activity and therefore, atypical antipsychotics can have inverse agonistic effects. It is hypothesized that decreasing the activity of 5-HT2 receptor carrying medium spiny neurons (MSNs) within the dorsal striatum represents the mechanism showing how atypical antipsychotics have limited ability to cause tardive dyskinesia.
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