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Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

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Abstract

Rationale

Central administration of corticotropin-releasing factor (CRF) elicits a specific pattern of behavioral responses resembling a stress-like state and is anxiogenic in rodent models of anxiety.

Objectives

Specific behaviors evoked by the administration of CRF were measured. The roles of CRF receptor subtypes and that of serotonergic and noradrenergic systems in mediating these responses were studied.

Materials and methods

Burying, grooming, and head shakes were quantified in rats following intracerebroventricular administration of CRF and urocortin II and after pretreatment with antagonists. The role of forebrain norepinephrine in the behavioral responses to CRF (0.3 μg) was examined following pretreatment with the neurotoxin DSP-4 and that of serotonin after depletion using systemic administration of para-chlorophenylalanine (p-CPA).

Results

CRF at 0.3 and 3.0 μg caused robust increases in burying, grooming, and head shakes, but urocortin II was ineffective. Pretreatment with either antalarmin or propranolol significantly attenuated the CRF-evoked behaviors. Destruction of forebrain norepinephrine pathways blocked spontaneous burying behavior elicited by CRF and conditioned burying directed towards an electrified shock probe. In contrast, depletion of 5-HT selectively attenuated CRF-evoked grooming.

Conclusions

Overt behavioral responses produced by CRF, burying, grooming, and head shakes appeared to be mediated through the CRF1 receptor. Spontaneous burying behavior evoked by CRF or conditioned burying directed towards a shock probe was disrupted by lesion of the dorsal noradrenergic bundle and may represent anxiety-like behavior caused by CRF activation of the locus ceruleus. In contrast, CRF-evoked increases in grooming were dependent on serotonin.

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Acknowledgments

This research was supported by USPHS grants MH40008 and MH58250. The authors thank Dr. Candace Hoffmann and Dr. Brian Hoshaw for their development of the conditioned burying test.

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Authors and Affiliations

  1. Department of Psychiatry, University of Pennsylvania, 125 South 31st Street, Room 2204, Philadelphia, PA, 19104, USA

    Owen Howard, Tiffany E. Hill & Irwin Lucki

  2. Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Owen Howard & Irwin Lucki

  3. Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Gregory V. Carr

  4. Department of Pharmacology, National University of Ireland, Galway, Ireland

    Owen Howard

  5. Department of Anesthesiology, Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Rita J. Valentino

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Correspondence to Irwin Lucki.

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Howard, O., Carr, G.V., Hill, T.E. et al. Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats. Psychopharmacology 199, 569–582 (2008). https://doi.org/10.1007/s00213-008-1179-7

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