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


OBJECTIVE
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.
Tucci
Sonia
S
Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, UK. sonia.tucci@kci.ac.uk
Cheeta
Survjit
S
Seth
Pallab
P
File
Sandra E
SE
D000818:Animals; D001007:Anxiety; D003213:Conditioning, Psychological / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D007398:Interpersonal Relations; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D018722:Nicotinic Agonists; D010446:Peptide Fragments; D009538:Nicotine; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)