Antipsychotic pathway genes with expression altered in opposite direction by antipsychotics and amphetamine.
To develop a new strategy for identifying possible psychotic- or antipsychotic-related pathway genes, rats were treated with clinical doses of haloperidol and clozapine for 4 days, and the altered expression of genes was compared with the genes altered in expression after amphetamine sensitization. The objective was to identify genes with expression altered in the same direction by haloperidol and clozapine but in the opposite direction in the amphetamine-sensitized rat striatum. These criteria were met by 21 genes, consisting of 15 genes upregulated by amphetamine, and 6 genes downregulated by amphetamine. Of the 21 genes, 15 are not presently identified, and only 3 genes (cathepsin K, GRK6, and a gene with accession number AI177589) are located in chromosome regions known to be associated with schizophrenia.
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Françoise
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Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Tallerico
Teresa
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Seeman
Philip
P
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002874:Chromosome Mapping; D003024:Clozapine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D014150:Antipsychotic Agents; D015259:Dopamine Agents; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000661:Amphetamine; D003024:Clozapine; D006220:Haloperidol