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Author Notes:

Address correspondence and reprint requests to Scott E. Hemby, PhD, Yerkes National Primate Research Center, 954 Gatewood Road, NE, Atlanta, GA 30329, USA; Email: shemby@pharm.emory.edu

We thank Drs. Chris Muly and Bill Freeman for their helpful comments and suggestions.

The Emory University Health Sciences Center Microarray Facility provided the cDNA clones.

Subjects:

Research Funding:

This research was supported in part by grants from the National Institute on Drug Abuse (DA13772, SEH; DA15941, WHF) and the Stanley Research Foundation (SEH).

Keywords:

  • glutamate receptors
  • haloperidol
  • laser capture microdissection
  • single cell gene expression
  • substantia nigra
  • ventral tegmental area

Time-dependent changes in gene expression profiles of midbrain dopamine neurons following haloperidol administration

Tools:

Journal Title:

Journal of Neurochemistry

Volume:

Volume 87, Number 1

Publisher:

, Pages 205-219

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Antipsychotic drugs require a treatment regimen of several weeks before clinical efficacy is achieved in patient populations. While the biochemical mechanisms underlying the delayed temporal profile remain unclear, molecular adaptations in specific neuroanatomical loci are likely involved. Haloperidol-induced changes in gene expression in various brain regions have been observed; however, alterations in distinct neuronal populations have remained elusive. The present study examined changes in gene expression profiles of ventral tegmental area (VTA) and substantia nigra (SN) tyrosine hydroxylase immunopositive neurons following 1, 10 or 21 days of haloperidol administration (0.5 mg/kg/day). Macroarrays were used to study the expression of receptors, signaling proteins, transcription factors and pre- and post-synaptic proteins. Data were analyzed using conventional statistical procedures as well as self-organizing maps (SOM) to elucidate conserved patterns of expression changes. Results show statistically significant haloperidol-induced and time-dependent alterations in 17 genes in the VTA and 25 genes in the SN, including glutamate and GABA receptor subunits, signaling proteins and transcription factors. SOMs revealed distinct patterns of gene expression changes in response to haloperidol. Understanding how gene expression is altered over a clinically relevant time course of haloperidol administration may provide insight into the development of antipsychotic efficacy as well as the underlying pathology of schizophrenia.

Copyright information:

© 2003 International Society for Neurochemistry

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