Ventral hippocampal α7 nicotinic receptor blockade and chronic nicotine effects on memory performance in the radial-arm maze

Abstract

Chronic nicotine administration has been shown to significantly improve working memory. Nicotinic involvement in memory function critically involves the ventral hippocampus. Local ventral hippocampal infusions of the nicotinic antagonists mecamylamine, dihydro-β-erythroidine (DHβE) and methyllycaconitine (MLA) significantly impair working memory. The impairment caused by hippocampal infusion of the α4β2 antagonist DHβE is reversed by chronic systemic nicotine. This study determined the interaction of chronic systemic nicotine with acute ventral hippocampal infusions of the α7 antagonist MLA. Adult female Sprague–Dawley rats were trained on an 8-arm radial maze working memory task. Then they underwent ventral hippocampal cannulation and received sc implants of minipumps delivering nicotine (0 or 5 mg/kg/day for 28 days). Acute ventral hippocampal infusions of MLA (0, 4.88, 14.64 and 43.92 μg/side) were given during 3–4 weeks of chronic nicotine. MLA caused a significant dose-related memory impairment. In the rats not receiving nicotine, the 14.64 and 43.92 μg/side MLA doses caused significant memory impairment. Chronic systemic nicotine exposure did not block the MLA-induced memory impairment. Comparing the current results with MLA with previous results with DHβE, equimolar ventral hippocampal DHβE more effectively impaired memory than MLA, but the DHβE-induced impairment was more effectively reversed by chronic systemic nicotine administration.