Clozapine and haloperidol differentially regulate dendritic spine formation and synaptogenesis in rat hippocampal neurons - PubMed (original) (raw)
Comparative Study
doi: 10.1016/j.mcn.2006.05.007. Epub 2006 Jul 17.
Affiliations
- PMID: 16844384
- DOI: 10.1016/j.mcn.2006.05.007
Comparative Study
Clozapine and haloperidol differentially regulate dendritic spine formation and synaptogenesis in rat hippocampal neurons
H M Critchlow et al. Mol Cell Neurosci. 2006 Aug.
Abstract
Antipsychotic drugs are the primary therapeutic treatment for schizophrenia. In addition to their dopaminergic/serotonergic function, atypical antipsychotics differ from conventional antipsychotics in the way they affect glutamatergic receptor function. A cellular correlate of this may be the modulation of dendritic spines (DS). Here, we demonstrate that in rat dissociated hippocampal neurons 1.0 microM clozapine administration increased DS-enriched protein spinophilin by 70%, increased post-synaptic protein shank1a puncta density by 26% and increased overall primary dendrite DS density by 59%. Filopodia and mushroom DS were particularly affected by clozapine. Conversely, 0.1 microM haloperidol decreased spinophilin protein by 40%, caused a 25% decrease in shank1a puncta and reduced the numbers of filopodia. In contrast, neither haloperidol nor clozapine induced any change in the levels of the pre-synaptic protein synapsin. This indicates that clozapine and haloperidol differentially regulate DS and post-synaptic plasticity. These findings may provide a molecular and cellular correlate to the superior therapeutic profile of clozapine when compared with haloperidol.
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