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Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans

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Abstract

Rationale

LY354740, a structural analogue of glutamate that shows specificity at the mGluR2/3 receptor, has anxiolytic effects in animal models.

Objective

This study investigated the anxiolytic effects of LY354740 in humans using the fear-potentiated startle reflex methodology.

Methods

Subjects were given either placebo (n=16), 20 mg LY354740 (n=15), or 200 mg LY354740 (n=13). The fear-potentiated startle tests examined startle potentiation to shock anticipation and to darkness.

Results

Consistent with previous results, startle was increased by threat of shock and by darkness. LY354740 did not affect baseline startle. Correspondingly, subjects did not report LY354740 to be sedative. LY354740 significantly reduced the increase in startle magnitude during shock anticipation, but not during darkness. Subjective reports of state anxiety and negative affectivity during the fear-potentiated startle tests were also reduced in a dose-dependent manner by LY354740.

Conclusions

These results suggest that LY354740 has an anxiolytic profile in humans without being sedative.

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Acknowledgements

The authors acknowledge Lilly Research Laboratories for their financial assistance and for providing LY354740. The work was conducted at Yale University School of Medicine, Department of Psychiatry, New Haven, Conn., USA.

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Authors and Affiliations

  1. NIMH/NIH/DHHS, Mood and Anxiety Disorder Program, 15K North Drive, MSC 2670, Bethesda, MD 20892-2670, USA

    Christian Grillon

  2. Connecticut VA Medical Center, 950 Campbell Avenue, West Haven, CT 06516, USA

    Jeremy Cordova & Charles A. Morgan, III

  3. Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN 46285, USA

    Louise R. Levine

Authors
  1. Christian Grillon
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  2. Jeremy Cordova
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  3. Louise R. Levine
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  4. Charles A. Morgan, III
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Correspondence to Christian Grillon.

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Grillon, C., Cordova, J., Levine, L.R. et al. Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology 168, 446–454 (2003). https://doi.org/10.1007/s00213-003-1444-8

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  • DOI: https://doi.org/10.1007/s00213-003-1444-8

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