Ventral hippocampal alpha 4 beta 2 nicotinic receptors and chronic nicotine effects on memory

Chronic nicotine administration has been repeatedly shown to facilitate wor king memory function in rats on the radial-arm maze. The critical neural me chanisms for this effect are still being discovered. The nicotinic nature o f the chronic nicotine induced memory improvement is supported by the findi ng that it is blocked by chronic mecamylamine co-infusion. The hippocampus also appears to be critically important. Hippocampal ibotenic acid lesions block the effect. Within the hippocampus, we have found that the alpha4 bet a2 nicotinic receptor subtype is involved in memory functioning. Acute vent ral hippocampal infusions of the alpha4 beta2 nicotinic antagonist dihydro- beta -erythroidine (DH betaE) significantly decreased working memory perfor mance in the radial-arm maze. The aim of the current study was to determine the importance of alpha4 beta2 receptors within the ventral hippocampus fo r the memory enhancing effects of chronic nicotine treatment. Adult female Sprague-Dawley rats were trained on the 8-arm radial maze and were cannulat ed bilaterally in the ventral hippocampus. Osmotic minipumps administering chronic nicotine at a rate of 5 mg per kg per day were also implanted in th e nicotine treatment rats. Control rats received saline-only minipumps. For a period of 4 weeks after surgery, each rat received bilateral hippocampal infusions of 0, 2, 6 and 18 mug per side of DH betaE and tested for memory performance on the radial-arm maze. Radial-arm maze choice accuracy was im paired by acute hippocampal DH betaE infusion in a dose-related fashion. Th is acute hippocampal DH betaE-induced choice accuracy impairment was elimin ated by chronic systemic nicotine infusion. Chronic nicotine in combination with acute vehicle hippocampal infusion was not seen to alter choice accur acy. Response latency was not found to be altered by acute hippocampal DH b etaE in the absence of chronic nicotine administration, but it did attenuat e the response latency reduction induced by chronic nicotine infusion. Wet dog shakes were not found to be affected by hippocampal DH betaE when given without chronic nicotine. Wet dog shakes were significantly increased by c hronic nicotine infusion. Intra-hippocampal DH betaE significantly potentia ted this effect. The results from the current study reinforce the hypothesi s that ventral hippocampal alpha4 beta2 nicotinic receptors are important f or memory function. These receptors may also have a role to play in the dev elopment of other aspects of behavior associated with chronic nicotine trea tment. (C) 2000 Published by Elsevier Science Ltd.