title: Novel drug-regulated transcriptional networks in brain reveal pharmacological properties of psychotropic drugs.
abstract: BACKGROUND
  Despite their widespread use, the biological mechanisms underlying the efficacy of psychotropic drugs are still incompletely known; improved understanding of these is essential for development of novel more effective drugs and rational design of therapy. Given the large number of psychotropic drugs available and their differential pharmacological effects, it would be important to establish specific predictors of response to various classes of drugs.
  
  
  RESULTS
  To identify the molecular mechanisms that may initiate therapeutic effects, whole-genome expression profiling (using 324 Illumina Mouse WG-6 microarrays) of drug-induced alterations in the mouse brain was undertaken, with a focus on the time-course (1, 2, 4 and 8 h) of gene expression changes produced by eighteen major psychotropic drugs: antidepressants, antipsychotics, anxiolytics, psychostimulants and opioids. The resulting database is freely accessible at http://www.genes2mind.org. Bioinformatics approaches led to the identification of three main drug-responsive genomic networks and indicated neurobiological pathways that mediate the alterations in transcription. Each tested psychotropic drug was characterized by a unique gene network expression profile related to its neuropharmacological properties. Functional links that connect expression of the networks to the development of neuronal adaptations (MAPK signaling pathway), control of brain metabolism (adipocytokine pathway), and organization of cell projections (mTOR pathway) were found.
  
  
  CONCLUSIONS
  The comparison of gene expression alterations between various drugs opened a new means to classify the different psychoactive compounds and to predict their cellular targets; this is well exemplified in the case of tianeptine, an antidepressant with unknown mechanisms of action. This work represents the first proof-of-concept study of a molecular classification of psychoactive drugs.
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of Sciences, Smętna 12, PL 31-343, Kraków, Poland. michkor@if-pan.krakow.
authors.forename: Michal
authors.initials: M
authors.lastname: Korostynski
authors.forename: Marcin
authors.initials: M
authors.lastname: Piechota
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Dzbek
authors.forename: Wiktor
authors.initials: W
authors.lastname: Mlynarski
authors.forename: Klaudia
authors.initials: K
authors.lastname: Szklarczyk
authors.forename: Barbara
authors.initials: B
authors.lastname: Ziolkowska
authors.forename: Ryszard
authors.initials: R
authors.lastname: Przewlocki
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D019295:Computational Biology; D030541:Databases, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011619:Psychotropic Drugs / Q000494:pharmacology*; D059467:Transcriptome
chemical_list: D011619:Psychotropic Drugs