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Effects of antipsychotic drugs on the expression of synaptic proteins and dendritic outgrowth in hippocampal neuronal cultures
Author(s) -
Park Sung Woo,
Lee Chan Hong,
Cho Hye Yeon,
Seo Mi Kyoung,
Lee Jung Goo,
Lee Bong Ju,
Seol Wongi,
Kee Baik Seok,
Kim Young Hoon
Publication year - 2013
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.21634
Subject(s) - haloperidol , aripiprazole , quetiapine , synaptophysin , synaptic plasticity , typical antipsychotic , synapse , pharmacology , neuroscience , olanzapine , hippocampal formation , antipsychotic , atypical antipsychotic , chemistry , biology , schizophrenia (object oriented programming) , medicine , psychology , receptor , psychiatry , dopamine , immunohistochemistry
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. Synapse 67:224–234, 2013. © 2013 Wiley Periodicals, Inc.