Long-Term Effects of Iloperidone on Cerebral Serotonin and Adrenoceptor Subtypes.
J Mol Neurosci
; 66(1): 59-67, 2018 Sep.
Article
em En
| MEDLINE
| ID: mdl-30091081
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
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Antipsicóticos
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Córtex Cerebral
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Receptores Adrenérgicos alfa
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Receptor 5-HT1A de Serotonina
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Receptor 5-HT2A de Serotonina
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Isoxazóis
Limite:
Animals
Idioma:
En
Revista:
J Mol Neurosci
Ano de publicação:
2018
Tipo de documento:
Article