[en] Changes in dopamine (DA) D-1, D-2, D-3, and D-4 receptors and serotonin 5-HT1A and 5-HT2A 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 D2 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-HT1A and decreased 5-HT2A 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 D2 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, receptors in CPu and NAc. JL 13 as well as other antipsychotic agents did not alter levels of forebrain D3 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 anti psychotic drug. (c) 2006Wiley-Liss, Inc.
Disciplines :
Neurosciences & behavior
Author, co-author :
Moran-Gates, Taylor; Massachusetts General Hospital > McLean Division > Mailman Research Center
Massari, Carla; Massachusetts General Hospital > McLean Division > Mailman Research Center
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