Long-Term Effects of Iloperidone on Cerebral Serotonin and Adrenoceptor Subtypes
| Autor: | Frank I. Tarazi, Yong Kee Choi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.drug_class Atypical antipsychotic Nucleus accumbens Pharmacology Hippocampus Basal Ganglia Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience Iloperidone 0302 clinical medicine Piperidines Neurotransmitter receptor Animals Medicine Receptor Serotonin 5-HT2A Receptor Prefrontal cortex 5-HT receptor Cerebral Cortex business.industry Isoxazoles General Medicine Receptors Adrenergic alpha Rats 030227 psychiatry nervous system Receptor Serotonin 5-HT1A Serotonin business 030217 neurology & neurosurgery Antipsychotic Agents medicine.drug |
| Zdroj: | Journal of Molecular Neuroscience. 66:59-67 |
| ISSN: | 1559-1166 0895-8696 |
| Popis: | The atypical antipsychotic drug iloperidone has high affinity for a wide range of neurotransmitter receptors, including serotonin and adrenoceptors. We examined the long-term effects of multiple doses of iloperidone (0.5, 1.5, or 5 mg/kg) on serotonin (5-HT) 5-HT1A, 5-HT2A receptor subtypes, and adrenoceptors α1 and α2 subtypes. Rats received daily intraperitoneal injections of different doses of iloperiodone or vehicle for 4 weeks. Receptor autoradiography quantified the levels of 5-HT and adrenoceptors in medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), caudate putamen (CPu), nucleus accumbens (NAc), and hippocampal CA1 (HIP-CA1) and CA3 (HIP-CA3) regions. Four weeks of iloperidone treatment significantly and dose-dependently increased 5-HT1A and decreased 5-HT2A receptors in the MPC and DFC. Higher doses of iloperidone (1.5 and 5 mg/kg) increased 5-HT1A and decreased 5-HT2A receptors in HIP-CA1 and HIP-CA3 regions. In addition, repeated iloperidone treatment produced significant increases in α1- and α2-adrenoceptors in MPC, DFC, HIP-CA1, and HIP-CA3 regions. No changes in 5-HT and adrenoceptors were observed in other brain regions examined. These results suggest that long-term iloperidone treatment exerts region- and dose-specific effects on forebrain 5-HT and adrenoceptors, which may contribute to its therapeutic benefits in improving positive and negative symptoms of schizophrenia as well as maintaining a benign safety profile. |
| Databáze: | OpenAIRE |
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