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


CONCLUSIONS
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.
MacDonald
Matthew L
ML
Laboratory of Neuroplasticity, McLean Hospital, Belmont, Massachusetts 02478, USA.
Eaton
Molly E
ME
Dudman
Joshua T
JT
Konradi
Christine
C
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D016000:Cluster Analysis; D003342:Corpus Striatum / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism
D014150:Antipsychotic Agents; D012333:RNA, Messenger