Chronic nicotine working and reference memory effects in the 16-arm radial maze: interactions with D1 agonist and antagonist drugs |
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Authors: | Edward D Levin Paul Kim Robin Meray |
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Institution: | (1) Department of Psychiatry, Neurobehavioral Research Laboratory, Duke University Medical Center, Box #3412, 27710 Durham, NC, USA |
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Abstract: | Chronic nicotine infusion has been found in a series of studies in our laboratory to significantly improve choice accuracy
of rats in the eight-arm radial maze. The current study was designed to compare the effects of chronic nicotine infusion on
working and reference memory in a 16-arm radial maze. Nicotine was administered to female Sprague-Dawley rats at approximately
5 mg/kg per day SC via osmotic minipumps. Controls received saline infusions. Chronic nicotine infusion significantly lowered
the number of working memory errors compared to controls, whereas the number of reference memory erros was not significantly
affected. The modest nicotine-induced reduction in working memory errors was seen as a main effect over the 4 weeks of infusion,
but the clearest effect was seen in weeks 3–4 of nicotine administration. For the 2 weeks after withdrawal, the nicotine effect
was no longer evident. Acute D1 challenges were given with the D1 agonist dihydrexidine (0, 0.25, 0.5 and 1 mg/kg) and the D1 antagonist SCH 23390 (0, 0.005, 0.015 and 0.05 μg/kg) during weeks 3–4 of chronic nicotine administration and weeks 1–2 after
withdrawal from nicotine. Dihydrexidine caused a modest dose-related increase in reference memory errors but not working memory
errors in the nicotine-treated, but not the control rats. The D1 antagonist SCH 23390 caused a modest though significant decrease in reference memory errors but not working memory errors
in the control, but not the nicotine-treated rats. The behavioral specificity of chronic nicotine infusion was demonstrated
with selective improvement in working memory function. Pharmacological interactions were seen with chronic nicotine treatment
increasing responsivity to D1 agonist and decreasing responsivity to a D1 antagonist with regard to reference memory. The mechanisms of this interaction are still undiscovered. |
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Keywords: | Nicotine SCH 23390 Dihydrexidine Memory Working memory Reference memory Radial-arm maze D1 Dopamine |
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