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Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes

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Abstract

Rationale

Corticotropin-releasing factor (CRF) produces anxiety-like and aversive effects when infused directly into the various regions of the brain, including the bed nucleus of the stria terminalis (BNST). However, the CRF receptor subtypes within the BNST mediating these phenomena have not been established.

Objectives

We used selective CRF receptor antagonists to determine the receptor subtypes involved in the anxiogenic-like and aversive effects CRF in the BNST.

Materials and methods

Male Long–Evans rats were bilaterally infused with CRF (0.2 or 1.0 nmol) either alone or in combination with the CRF1 receptor antagonist CP154,526 or the CRF2 receptor antagonist anti-sauvagine 30 (AS30) before behavioral testing in the elevated plus maze or place conditioning paradigms.

Results

Intra-BNST administration of CRF produced a dose-dependent reduction in open arm entries and open arm time in the elevated plus maze, indicating an anxiogenic-like effect. These effects were inhibited by co-infusion of CP154,526 but not of AS30, indicating that the anxiogenic-like effects of CRF in the BNST are mediated by CRF1 receptors. Place conditioning with intra-BNST administration of CRF produced a dose-dependent aversion to the CRF-paired environment that was prevented by co-infusion of either CP154,526 or AS30, indicating that both CRF receptor subtypes mediate the aversive effects of this peptide. Intra-BNST infusions of the CRF receptor antagonists alone produced no effects in either behavioral paradigm.

Conclusions

CRF1 receptors in the BNST mediate the anxiogenic-like effects of CRF in this region, whereas both CRF1 and CRF2 receptor subtypes mediate the conditioned aversive effects of this peptide within the BNST.

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Acknowledgements

This work was supported by Public Health Service grants AA13276 and AA013852 to MFO, the Charleston Alcohol Research Center (AA010761), and funds provided by the State of California for medical research on alcohol and substance abuse through the University of California at San Francisco. The authors wish to thank Dr. Tom Greenberg and Dr. Eric Zorrilla of The Scripps Research Institute for technical advice on elevated plus maze procedures. The experiments described herein were conducted in accordance with the current laws of the Food and Drug Administration of the United States of America. Portions of these data have been presented previously in abstract form (Sahuque et al. 2004).

Author information

Authors and Affiliations

  1. Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco, Emeryville, CA, 94608, USA

    Lacey L. Sahuque, Andrew J. Mcgeehan, Jennifer R. Kinder & Patricia H. Janak

  2. Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, P.O. Box 250861, Charleston, SC, 29425, USA

    Erika F. Kullberg, Megan P. Hicks, Mary G. Blanton & M. Foster Olive

Authors
  1. Lacey L. Sahuque
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  2. Erika F. Kullberg
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  3. Andrew J. Mcgeehan
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  4. Jennifer R. Kinder
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  5. Megan P. Hicks
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  6. Mary G. Blanton
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  7. Patricia H. Janak
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  8. M. Foster Olive
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Corresponding author

Correspondence to M. Foster Olive.

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Sahuque, L.L., Kullberg, E.F., Mcgeehan, A.J. et al. Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes. Psychopharmacology 186, 122–132 (2006). https://doi.org/10.1007/s00213-006-0362-y

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  • DOI: https://doi.org/10.1007/s00213-006-0362-y

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