The effects of chronic nicotine on spatial learning and bromodeoxyuridine incorporation into the dentate gyrus of the rat.
BACKGROUND
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.
Scerri
Charles
C
Section of Psychiatry and Behavioural Sciences, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY, UK.
Stewart
Caroline A
CA
Breen
Kieran C
KC
Balfour
David J K
DJ
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D011939:Mental Recall / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009949:Orientation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014029:Tobacco Use Disorder / Q000503:physiopathology*
D001973:Bromodeoxyuridine