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Long-Term Effects of Iloperidone on Cerebral Serotonin and Adrenoceptor Subtypes

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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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Acknowledgments

Supported by Novartis Pharmaceuticals (FIT). The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA, USA

    Yong Kee Choi & Frank I. Tarazi

  2. Mailman Research Center, McLean Hospital, Belmont, MA, USA

    Yong Kee Choi & Frank I. Tarazi

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  1. Yong Kee Choi
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  2. Frank I. Tarazi
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Correspondence to Frank I. Tarazi.

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Choi, Y.K., Tarazi, F.I. Long-Term Effects of Iloperidone on Cerebral Serotonin and Adrenoceptor Subtypes. J Mol Neurosci 66, 59–67 (2018). https://doi.org/10.1007/s12031-018-1133-z

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  • DOI: https://doi.org/10.1007/s12031-018-1133-z

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