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Long‐term effects of JL 13, a potential atypical antipsychotic, on rat dopamine and serotonin receptor subtypes
Author(s) -
MoranGates Taylor,
Massari Carla,
Graulich Amaury,
Liégeois JeanFrançois,
Tarazi Frank I.
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20972
Subject(s) - atypical antipsychotic , clozapine , dopamine receptor d2 , typical antipsychotic , antipsychotic , olanzapine , dopamine , receptor , pharmacology , nucleus accumbens , medicine , psychology , endocrinology , chemistry , schizophrenia (object oriented programming) , psychiatry
Changes in dopamine (DA) D 1 , D 2 , D 3 , and D 4 receptors and serotonin 5‐HT 1A and 5‐HT 2A receptors in rat forebrain regions were autoradiographically quantified after continuous infusion of JL 13 [(5‐(4‐methylpiperazin‐1‐yl)‐8‐chloro‐pyrido[2,3‐ b ][1,5]benzoxazepine fumarate] for 28 days with osmotic minipumps and compared with the effects of other typical (fluphenazine) and atypical (clozapine, olanzapine, and risperidone) antipsychotic drugs from previous studies. Similar to other typical and atypical antipsychotics, JL 13 increased labeling of D 2 receptors in medial prefrontal cortex (MPC) and hippocampus (HIP) and D 4 receptors in nucleus accumbens (NAc), caudate‐putamen (CPu), and HIP. In addition, JL 13 increased 5‐HT 1A and decreased 5‐HT 2A receptors in MPC and dorsolateral frontal cortex (DFC), an effect shared by atypical antipsychotics, and may contribute to their psychopharmacological properties. Clozapine and JL 13, but not other antipsychotics, spared D 2 receptors in CPu, which may reflect their ability to induce minimal extrapyramidal side effects. In addition, JL 13 but not other typical and atypical antipsychotic drugs increased abundance of D 1 receptors in CPu and NAc. JL 13 as well as other antipsychotic agents did not alter levels of forebrain D 3 receptors. An atypical‐like profile of JL 13 on DA and 5‐HT receptor subtypes should encourage further development of this compound as a novel atypical antipsychotic drug. © 2006 Wiley‐Liss, Inc.