CHRONIC NICOTINE WORKING AND REFERENCE MEMORY EFFECTS IN THE 16-ARM RADIAL MAZE - INTERACTIONS WITH D-1 AGONIST AND ANTAGONIST DRUGS

Chronic nicotine infusion has been found in a series of studies in our laboratory to significantly improve choice accuracy of rats in the ei ght-arm radial maze. The current study was designed to compare the eff ects of chronic nicotine infusion on working and reference memory in a 16-arm radial maze. Nicotine was administered to female Sprague-Dawle y rats at approximately 5 mg/kg per day SC via osmotic minipumps. Cont rols received saline infusions. Chronic nicotine infusion significantl y lowered the number of working memory errors compared to controls, wh ereas the number of reference memory errors was not significantly affe cted. The modest nicotine-induced reduction in working memory errors w as seen as a main effect over the 4 weeks of infusion, but the dearest effect was seen in weeks 3-4 of nicotine administration. For the 2 we eks after withdrawal, the nicotine effect was no longer evident. Acute D-1 challenges were given with the D-1 agonist dihydrexidine (0, 0.25 , 0.5 and 1 mg/kg) and the D-1 antagonist SCH 23390 (0, 0.005, 0.015 a nd 0.05 mu g/kg) during weeks 3-4 of chronic nicotine administration a nd weeks 1-2 after withdrawal from nicotine. Dihydrexidine caused a mo dest dose-related increase in reference memory errors but not working memory errors in the nicotine-treated, but not the control rats. The D -1 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 chro nic nicotine infusion was demonstrated with selective improvement in w orking memory function. Pharmacological interactions were seen with ch ronic nicotine treatment increasing responsivity to D-1 agonist and de creasing responsivity to a D-1 antagonist with regard to reference mem ory. The mechanisms of this interaction are still undiscovered.