Anxiety-like behavior during nicotine withdrawal predict subsequent nicotine consumption in adolescent C57BL/6 mice.

We have previously demonstrated that anxiety-like behavior assessed in the elevated plus maze does not predict subsequent nicotine consumption in naïve adolescent mice. However, an association between anxiety and relapse to drug use has been suggested. In the present study, we investigated whether anxiety levels during nicotine withdrawal predict subsequent nicotine consumption in adolescent mice. C57BL/6 mice were either exposed to (-)-nicotine-free base (nicotine, 50mug/ml) or tap water (water) from postnatal day 30 to 45 (PN30-PN45, priming period). By the end of PN48, all animals were submitted to the elevated plus maze and classified as either having high (HiAnx) or low (LoAnx) levels of anxiety. Immediately after finishing the test, all animals were returned to their home cages and were given a free choice (from PN49 to PN55, free-choice period) between two bottles, one containing a nicotine solution (10mug/ml) and the other tap water. Nicotine consumption during the free-choice period was affected by the priming treatment (nicotine or water) in a way that was dependent on the anxiety level (HiAnx or LoAnx): the nicotine HiAnx group had lower nicotine consumption than the other groups. No differences were observed between the nicotine LoAnx, water HiAnx and water LoAnx groups. The present study provides experimental evidence for the role of anxiety on the regulation of drug consumption. Specifically, our results suggest that the anxiety-like behavior during nicotine withdrawal is associated with subsequent nicotine self-administration.