Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News and Commentary
  • Published:

Antidepressants and gene expression profiling: how to SNARE novel drug targets

The Pharmacogenomics Journal volume 2, pages 346–348 (2002)Cite this article

A latency period of several weeks before the onset of antidepressant drug effects represents a considerable clinical challenge in the treatment of depression. As the detailed mechanism of action of antidepressant drugs continues to be enigmatic, studies have shifted focus from adaptive changes in neurotransmitter release, uptake, and metabolism to modulation of gene expression, synaptic plasticity, neurogenesis, and neuronal survival. In this issue of The Pharmacogenomics Journal, however, Yamada et al1 make a strong argument for a critical role of VAMP2/synaptobrevin-2, a component of the SNARE (SNAP receptors) core complex in the presynaptic nerve terminal, in the molecular mechanism underlying antidepressant drug-induced adaptive neuronal changes. Not only chronic treatment with antidepressants, including the prototypic tricyclic imipramine and the selective serotonin reuptake inhibitor (SSRI) sertraline, but also electroconvulsive treatment (ECT) increased the expression of VAMP2/synaptobrevin-2 in rat frontal cortex, while other components of the SNARE complex, including syntaxin-1 and SNAP-25, remained unchanged.

Despite the attractiveness of this concept, several additional and exceedingly complex but tightly coordinated gene regulatory events are likely to further reinforce antidepressant-induced neuroadaptive changes resulting in reliable treatment responses. Direct support for this notion is provided by the same group who previously reported increased expression of CSP, which is thought to modulate presynaptic calcium channel activity and, as a result, synaptic neurotransmitter release by interacting with VAMP2/synaptobrevin-2.4 Nonetheless, the molecular mechanism of selective changes in the expression and presumably function of only two components of the neurotransmitter release machinery remains unsolved. Elucidation of the mechanisms will require identification of specific intracellular signaling pathways that activate a distinct set of transcription factors which have the potential to bind selectively and in a spatiotemporally defined pattern to the transcriptional regulatory region of the target genes. A detailed analysis of the molecular biology underlying neuronal communication, particularly with respect to defining the transfer of receptor-detected signals across cell membranes to intracellular effectors and regulation of gene expression, has been among the most thought-provoking advances related to the concept of antidepressant-induced neural adaptation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Yamada M et al . Pharmacogenomics J 2002 2: 377–382

  2. Südhof TC . Nature 1995 375: 645–653

  3. Mochida S . Neurosci Res 2000 36: 175–182

  4. Yamada M et al . Neurosci Lett 2001 301: 183–186

  5. Blier P, de Montigny C . Biol Psychiatry 1998 44: 313–323

  6. Lesch KP et al . Mol Brain Res 1993 17: 31–35

  7. Benmansour S et al . J Neurosci 2002 22: 6766–6772

  8. Lesch KP et al . Psychopharmacology 1991 105: 415–420

  9. Nibuya M et al . J Neurosci 1996 16: 2365–2372

  10. Morinobu S et al . Synapse 1997 25: 313–320

  11. Lesch KP, Heils A . Int J Neuropsychopharmacol 2000 3: 67–79

  12. Kim SW et al . Mol Pharmacol 2002 61: 778–785

  13. Nibuya M et al . J Neurosci 1995 15: 7539–7547

  14. Vaidya VA et al . Neuroscience 1999 89: 157–166

  15. Malberg JE et al . J Neurosci 2000 20: 9104–9110

  16. Gould E . Neuropsychopharmacol 1999 21: 46S–51S

  17. Lesch KP . Eur J Neuropsychopharmacol 2001 11: 457–474

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Section of Molecular Psychobiology, University of Würzburg, Würzburg, Germany

    K-P Lesch & A Schmitt

Authors
  1. K-P Lesch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K-P Lesch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lesch, KP., Schmitt, A. Antidepressants and gene expression profiling: how to SNARE novel drug targets. Pharmacogenomics J 2, 346–348 (2002). https://doi.org/10.1038/sj.tpj.6500150

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.tpj.6500150

This article is cited by

Search

Advanced search

Quick links