The effects of chronic nicotine on spatial learning and bromodeoxyuridine incorporation into the dentate gyrus of the rat

Rationale: Nicotine is reported to improve learning and memory in experimental animals. Improved learning and memory has also been related to increased neurogenesis in the dentate gyrus (DG) of the hippocampal formation. Surprisingly, recent studies suggest that self-administered nicotine depresses cell proliferation in the DG. Objective: To test the hypothesis that the effects of nicotine on cell proliferation in the DG and learning and memory depend upon the nicotine dose administered. Methods: Rats were chronically infused from subcutaneous osmotic mini pumps with nicotine (0.25 or 4 mg kg(-1)day(-1)) or the saline vehicle for 10 days. Half the rats in each treatment group were trained to locate a hidden platform in a water maze task on days 4-7; a probe trial was performed on day 8. The remaining rats remained in their home cages. The effects of nicotine and of training in the water maze task on cell genesis in the DG were determined by measuring 5-bromo-2'-deoxyuridine (BrDU) uptake using fluorescence immunohistochemistry. Results: Training in the water maze task increased cell proliferation in the DG. Infusions of nicotine at 4 mg kg(-1) day(-1), but not 0.25 mg kg(-1) day(-1), decreased cell proliferation in both untrained animals and animals trained in the maze and impaired spatial learning. Conclusions: The data suggest that learning in the water maze task is impaired by higher doses of nicotine tested, and that this response may be related to reduced cell genesis in the DG.