PMID- 23335099 OWN - NLM STAT- MEDLINE DCOM- 20130903 LR - 20171116 IS - 1098-2396 (Electronic) IS - 0887-4476 (Linking) VI - 67 IP - 5 DP - 2013 May TI - Effects of antipsychotic drugs on the expression of synaptic proteins and dendritic outgrowth in hippocampal neuronal cultures. PG - 224-34 LID - 10.1002/syn.21634 [doi] AB - Recent evidence has suggested that atypical antipsychotic drugs regulate synaptic plasticity. We investigated whether some atypical antipsychotic drugs (olanzapine, aripiprazole, quetiapine, and ziprasidone) altered the expression of synapse-associated proteins in rat hippocampal neuronal cultures under toxic conditions induced by B27 deprivation. A typical antipsychotic, haloperidol, was used for comparison. We measured changes in the expression of various synaptic proteins including postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and synaptophysin (SYP). Then we examined whether these drugs affected the dendritic morphology of hippocampal neurons. We found that olanzapine, aripiprazole, and quetiapine, but not haloperidol, significantly hindered the B27 deprivation-induced decrease in the levels of these synaptic proteins. Ziprasidone did not affect PSD-95 or BDNF levels, but significantly increased the levels of SYP under B27 deprivation conditions. Moreover, olanzapine and aripiprazole individually significantly increased the levels of PSD-95 and BDNF, respectively, even under normal conditions, whereas haloperidol decreased the levels of PSD-95. These drugs increased the total outgrowth of hippocampal dendrites via PI3K signaling, whereas haloperidol had no effect in this regard. Together, these results suggest that the up-regulation of synaptic proteins and dendritic outgrowth may represent key effects of some atypical antipsychotic drugs but that haloperidol may be associated with distinct actions. CI - Copyright (c) 2013 Wiley Periodicals, Inc. FAU - Park, Sung Woo AU - Park SW AD - Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea. FAU - Lee, Chan Hong AU - Lee CH FAU - Cho, Hye Yeon AU - Cho HY FAU - Seo, Mi Kyoung AU - Seo MK FAU - Lee, Jung Goo AU - Lee JG FAU - Lee, Bong Ju AU - Lee BJ FAU - Seol, Wongi AU - Seol W FAU - Kee, Baik Seok AU - Kee BS FAU - Kim, Young Hoon AU - Kim YH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130214 PL - United States TA - Synapse JT - Synapse (New York, N.Y.) JID - 8806914 RN - 0 (Antipsychotic Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Disks Large Homolog 4 Protein) RN - 0 (Dlg4 protein, rat) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Synaptophysin) SB - IM MH - Animals MH - Antipsychotic Agents/*pharmacology MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cells, Cultured MH - Dendrites/*drug effects/metabolism MH - Disks Large Homolog 4 Protein MH - Gene Expression/*drug effects MH - Hippocampus/*cytology/metabolism MH - Intracellular Signaling Peptides and Proteins/genetics/*metabolism MH - Membrane Proteins/genetics/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Synaptophysin/genetics/*metabolism MH - Up-Regulation EDAT- 2013/01/22 06:00 MHDA- 2013/09/04 06:00 CRDT- 2013/01/22 06:00 PHST- 2012/10/17 00:00 [received] PHST- 2012/12/18 00:00 [accepted] PHST- 2013/01/22 06:00 [entrez] PHST- 2013/01/22 06:00 [pubmed] PHST- 2013/09/04 06:00 [medline] AID - 10.1002/syn.21634 [doi] PST - ppublish SO - Synapse. 2013 May;67(5):224-34. doi: 10.1002/syn.21634. Epub 2013 Feb 14.