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

Abstract

Chronic nicotine infusions have been found to significantly improve working memory performance in the radial-arm maze. This effect is blocked by co-infusions of the nicotinic antagonist mecamylamine. Acute nicotine injections also improve working memory performance in the radial-arm maze. This effect is also blocked by mecamylamine co-administration. Recent local infusions studies have demonstrated the importance of the ventral hippocampus for nicotinic involvement in memory. Local infusions of mecamylamine, DHbetaE or MLA impair working memory performance on the radial-arm maze. The current study was conducted to determine the importance of the ventral hippocampus for the chronic effects of nicotine. Rats were trained on the working memory task in an eight-arm radial maze. After acquisition they underwent either infusions of ibotenic acid lesions or vehicle infusions and received subcutaneous implants of osmotic minipumps that delivered either nicotine at a dose of 5 mg kg-1 day-1 or vehicle in a 2x2 design. The rats then were given 2 days of recovery and were tested on the radial-arm maze three times per week for the next 4 weeks. As seen in previous studies, in the sham lesioned group nicotine infusions caused a significant improvement in choice accuracy. In contrast no nicotine-induced improvement was seen in the rats after 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 significant improvement in working memory performance in the radial-arm maze after knife-cut lesions of the fimbria-fornix carrying the septo-hippocampal cholinergic innervation. Thus it appears that it is the postsynaptic nicotinic receptors in the ventral hippocampus which are critically important for the expression of the chronic nicotine induced working memory improvement.