Premium
Long‐term effects of iloperidone on cerebral dopamine receptor subtypes
Author(s) -
Kee Choi Yong,
Tarazi Frank I.
Publication year - 2018
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.22039
Subject(s) - nucleus accumbens , receptor , dopamine receptor d3 , dopamine , pharmacology , dopaminergic , dopamine receptor , chemistry , hippocampus , medicine , endocrinology
The atypical antipsychotic drug iloperidone has high affinity for a wide range of neurotransmitter receptors, including dopaminergic (DA), serotonergic, and adrenergic receptors. We examined the long‐term effects of multiple doses of iloperidone on DA D 1 , D 2 , D 3 , and D 4 receptor subtypes. Sprague‐Dawley adult rats ( n = 8/group) received daily intraperitoneal injections of iloperiodone (0.5, 1, or 5 mg/kg) or vehicle for 4 weeks. Receptor autoradiography quantified the levels of DA receptors in medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus (HIP). Four weeks of iloperidone treatment at 5 mg/kg significantly increased D 1 receptors in NAc (36%) and CPu (38%). Iloperidone (1.5 and 5 mg/kg) dose‐dependently increased D 2 receptors in MPC (37 and 47%) and HIP (32 and 40%). Only the high dose of iloperidone (5 mg/kg) increased D 2 receptors in NAc (39%) and CPu (38%). Repeated treatment with iloperidone (1.5 and 5 mg/kg) increased D 4 receptors in the NAc (39 and 78%), CPu (42 and 83%) and HIP (54 and 72%). The three doses of iloperidone failed to alter D 3 receptors in the brain regions examined in this study. These results suggest that iloperidone exerts region‐ and dose‐specific effects on forebrain DA receptor subtypes, which may contribute to its therapeutic benefits in improving the positive and negative symptoms of schizophrenia with minimal extrapyramidal side effects.