Antipsychotic drugs elevate mRNA levels of presynaptic proteins in the frontal cortex of the rat.

MacDonald ML, Eaton ME, Dudman JT, Konradi C
Biol Psychiatry. 2005 57 (9): 1041-51

PMID: 15860345 · PMCID: PMC2734482 · DOI:10.1016/j.biopsych.2005.01.022

BACKGROUND - Molecular adaptations are believed to contribute to the mechanism of action of antipsychotic drugs (APDs). We attempted to establish common gene regulation patterns induced by chronic treatment with APDs.

METHODS - Gene expression analysis was performed with the Affymetrix U34A array in the frontal cortex (FC) and the striatum of rats chronically treated with two concentrations of either clozapine or haloperidol. Key data were verified with real-time quantitative polymerase chain reaction.

RESULTS - Many genes in the FC affected by APD-treatment contribute to similar functions. mRNAs coding for synaptic vesicle docking- and microtubule-associated proteins were upregulated; mRNAs for serine-threonine protein phosphatases were downregulated, whereas the serine-threonine kinases protein kinase A, protein kinase C, and calcium/calmodulin kinase II alpha and IV were upregulated, indicating increased potential for protein phosphorylation. In the striatum, altered gene expression was less focused on genes of particular function or location, and the high concentration of haloperidol had a different gene expression profile than any of the other APD treatments.

CONCLUSION - We found an increase in the transcription of genes coding for proteins involved in synaptic plasticity and synaptic activity in the FC. We furthermore found that the gene expression profile of APDs is different between FC and striatum.

MeSH Terms (15)

Animals Antipsychotic Agents Cluster Analysis Corpus Striatum Frontal Lobe Gene Expression Male Microtubules Oligonucleotide Array Sequence Analysis Presynaptic Terminals Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Synaptic Vesicles

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