Haloperidol‐Induced Neuronal Apoptosis

• DOI: 10.1046/j.1471-4159.2000.0752327.x
• Publication Date: 2003-03-12T06:49:16Z
• Authors: Jai Sung Noh; Hyo Jung Kang; Eun Young Kim; Seonghyang Sohn; Young Ki Chung; Seung U. Kim; Byoung J. Gwag
• Keywords: Wortmannin

Abstract: We examined patterns and mechanisms of cell death inducedby haloperidol. Cortical cultures exposed to 10‐100 μ M haloperidol for 24 h underwent neuronal without injuring glia. Thedegenerating neurons showed hallmarks apoptosis, featuring bodyshrinkage, nuclear chromatin condensation aggregation, membranedisintegration with intact plasma membrane, prominent internucleosomal DNAfragmentation. Neither glutamate antagonists nor antioxidants prevented thehaloperidol‐induced apoptosis. The c‐Jun‐NH 2 ‐terminalprotein kinase p38 mitogen‐activated protein were activated within1 sustained over the next 3 following exposure corticalneurons 30 Haloperidol‐induced neuronalapoptosis was partially attenuated by 10‐30 PD169316, aselective inhibitor kinase. Inclusion 1μg/ml cycloheximide, a synthesis inhibitor, or 100 ng/ml insulinprevented activation both kinases subsequent death. Thepresent study demonstrates that cortical haloperidolundergo apoptosis depending on proteinkinase ‐terminal sensitive tocycloheximide insulin.