Corticotropin releasing factor antagonist, alpha-helical CRF(9-41), reverses nicotine-induced conditioned, but not unconditioned, anxiety

Psychopharmacology (Berl). 2003 May;167(3):251-6. doi: 10.1007/s00213-003-1403-4. Epub 2003 Apr 1.


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 alpha-helical CRF(9-41) 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 alpha-helical CRF(9-41). 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 alpha-helical CRF(9-41) (5 microg).

Results: alpha-Helical CRF(9-41) 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 alpha-helical CRF(9-41). 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety*
  • Conditioning, Psychological / drug effects*
  • Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Corticotropin-Releasing Hormone / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Interactions
  • Interpersonal Relations
  • Male
  • Motor Activity / drug effects
  • Nicotine / antagonists & inhibitors
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology
  • Peptide Fragments / pharmacology*
  • Rats
  • Time Factors


  • Nicotinic Agonists
  • Peptide Fragments
  • Nicotine
  • Corticotropin-Releasing Hormone
  • corticotropin releasing hormone (9-41)