EPIBATIDINE, A POTENT NICOTINIC AGONIST - EFFECTS ON LEARNING AND MEMORY IN THE RADIAL-ARM MAZE

Epibatidine is a potent nicotinic agonist originally isolated from fro g skin. Nicotine has been found in a variety of studies to improve wor king memory function in several different tests including the radial-a rm maze (RAM). The current studies were conducted to determine if epib atidine would affect learning and memory in the radial-arm maze. Three studies were conducted. In the first study, rats were pretrained on t he radial-arm maze and then given acute doses of epibatidine (0, 0.25, 0.5 and 1.0 mu g/kg) in a repeated measures counter-balanced design. Compared to memory performance either before or after the drug study, performance during the drug study was significantly improved. This was true even with the intercurrent saline injections. This may have resu lted from persisting effects of epibatidine administration. Because of this possibility of carryover effects the other studies both used bet ween subjects designs. In the second study the rats were given 0, 0.5 or 1.0 mu g/kg of epibatidine in a between subjects design throughout 24 sessions of RAM training. The rats given 0.5 mu g/kg had a trend to ward improved choice accuracy performance relative to control during t he middle phase of learning. The higher dose had no apparent effect. T o determine if the transience of the improvement caused by 0.5 mu g/kg of epibatidine was due to the chronicity of the treatment or the phas e of training a third study was conducted in which rats were pretraine d for 12 sessions and then were given 0.5 mu g/kg of epibatidine in a between subjects design for an additional 24 sessions of training. In this study when epibatidine was only given during the later phases of training no improvement was seen. In fact, a significant epibatidine d eficit was seen during the final phase of training. These studies show that the potent nicotinic agonist epibatidine can significantly impai r choice accuracy performance in the radial-arm maze. The expression o f its effect depends critically on when during training it is given.