Conditioned anxiety to nicotine.

Rationale: Despite its reinforcing properties nicotine has also been reported to produce anxiety in humans and anxiogenic effects in animal tests of anxiety.

Objective: The aims of this study were three-fold: (a) to investigate whether anxiety can be conditioned to cues associated with an acute anxiogenic dose of nicotine, (b) to investigate whether the conditioned anxiety is specific to a particular test of anxiety, and (c) to investigate whether nicotine pre-exposure influences the development of a conditioned anxiogenic effect.

Methods: An anxiogenic dose of nicotine was administered to rats either before or after experience with the social interaction (SI) test. The retention of a conditioned anxiogenic response was examined when the rats were re-tested undrugged in the SI test 24 h later. To test whether conditioned anxiety was test specific, rats that had been tested in the elevated plus-maze with an anxiogenic dose of nicotine were retested undrugged in the SI test 24 h later, and vice versa. We then examined the effects of 4 days or 4 weeks pre-exposure to nicotine on the development of a conditioned anxiogenic response in the SI test.

Results: Rats injected with nicotine (0.45 mg/kg s.c.) 5 min before the social interaction test spent significantly less time in SI, indicating an unconditioned anxiogenic effect than did vehicle-injected controls or rats injected with nicotine after the test. After 24 h when all groups were tested undrugged only those previously tested in SI after nicotine injection showed a significant conditioned anxiogenic effect. This conditioned anxiety was test specific. Rats injected with nicotine before the SI test did not show an anxiogenic response when tested 24 h later undrugged in the plus-maze, and vice versa. Furthermore, although 4 days exposure to nicotine (0.45 mg/kg s.c.) did not prevent the development of a conditioned anxiogenic response, 4 weeks self-administration of nicotine (total dose, 0.45 mg/kg i.v) in an operant chamber did not affect the acute anxiogenic response to nicotine in the SI test, but it did prevent the development of conditioned anxiety.

Conclusions: The present findings suggest that anxiety can be conditioned following exposure to an anxiogenic dose of nicotine, and that this anxiety is specific to the contextual cues associated with the SI test.