Ventral hippocampal ibotenic acid lesions block chronic nicotine-induced spatial working memory improvement in rats

Chronic nicotine infusions have been found to significantly improve working memory performance in the radial-arm maze. This effect is blocked by co-in fusions of the nicotinic antagonist mecamylamine. Acute nicotine injections also improve working memory performance in the radial-arm maze. This effec t is also blocked by mecamylamine co-administration. Recent local infusions studies have demonstrated the importance of the ventral hippocampus for ni cotinic involvement in memory. Local infusions of mecamylamine, DHPE or MLA impair working memory performance on the radial-arm maze. The current stud y was conducted to determine the importance of the ventral hippocampus for the chronic effects of nicotine. Rats were trained on the working memory ta sk in an eight-arm radial maze. After acquisition they underwent either inf usions of ibotenic acid lesions or vehicle infusions and received subcutane ous implants of osmotic minipumps that delivered either nicotine at a dose of 5 mg kg(-1) day(-1) or vehicle in a 2 X 2 design. The rats then were giv en 2 days of recovery and were tested on the radial-arm maze three times pe r week for the next 4 weeks. As seen in previous studies, in the sham lesio ned group nicotine infusions caused a significant improvement in choice acc uracy. In contrast no nicotine-induced improvement was seen in the rats aft er ibotenic acid lesions of the ventral hippocampus. The effect of nicotine was blocked even though this lesion did not cause a deficit in performance . Previous work showed that chronic nicotine infusion still caused a signif icant improvement in working memory performance in the radial-arm maze afte r knife-cut lesions of the fimbria-fornix carrying the septo-hippocampal ch olinergic innervation Thus it appears that it is the postsynaptic nicotinic receptors in the ventral hippocampus which are critically important for th e expression of the chronic nicotine induced working memory improvement. (C ) 1999 Elsevier Science B.V. All rights reserved.