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Corticotropin releasing factor antagonist, α-helical CRF9–41, reverses nicotine-induced conditioned, but not unconditioned, anxiety

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Abstract

Rationale

Unconditioned anxiogenic effects of nicotine have been observed in the social interaction (SI) test 5 min after injection of a low dose and both 5 min and 30 min after injection of a high dose. Conditioned anxiety has also been observed 24 h after testing in the SI with a high dose of nicotine.

Objectives

In order to determine whether these three anxiogenic effects shared a common mechanism, we investigated the role of corticotropin releasing factor (CRF). We therefore examined whether the CRF antagonist α-helical CRF9–41 could block these three anxiogenic effects of nicotine.

Methods

To test the unconditioned anxiogenic effects, pairs of male rats were tested in SI 5 min after s.c. vehicle or nicotine (0.1 mg/kg) or 30 min after s.c. vehicle or nicotine (0.45 mg/kg), and 30 min after i.c.v. artificial cerebrospinal fluid (aCSF) or α-helical CRF9–41. To test conditioned anxiety, rats were exposed to the SI test on day 1, 5 min after vehicle or nicotine (0.1 mg/kg). On day 2, they were re-tested in SI 30 min after i.c.v. aCSF or α-helical CRF9–41 (5 μg).

Results

α-Helical CRF9–41 did not block the unconditioned anxiogenic effect of either dose of nicotine. Nicotine (0.1 mg/kg, 5 min) elicited a conditioned anxiogenic response that was significantly reversed by α-helical CRF9–41. The CRF antagonist alone had no effect.

Conclusions

CRF is an important mediator of the conditioned anxiety to nicotine, but may not play a role in mediating the acute anxiogenic effects.

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Acknowledgements

This study was supported by a grant from the CONICIT-ULA, Venezuela. We are indebted to Dr. J. Rivier for the generous gift of α-helical CRF9–41 and to Dr A. Dunn for his advice.

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Authors and Affiliations

  1. Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, London, SE1 1UL, UK

    Sonia Tucci, Survjit Cheeta, Pallab Seth & Sandra E. File

  2. Department of Addictive Behaviour and Psychological Medicine, Cranmer Terrace, London, SW17 ORE, UK

    Survjit Cheeta

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  1. Sonia Tucci
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  2. Survjit Cheeta
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  3. Pallab Seth
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  4. Sandra E. File
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Correspondence to Sonia Tucci.

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Tucci, S., Cheeta, S., Seth, P. et al. Corticotropin releasing factor antagonist, α-helical CRF9–41, reverses nicotine-induced conditioned, but not unconditioned, anxiety. Psychopharmacology 167, 251–256 (2003). https://doi.org/10.1007/s00213-003-1403-4

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  • DOI: https://doi.org/10.1007/s00213-003-1403-4

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