NMDA systems in the amygdala and piriform cortex and nicotinic effects on memory function.

Abstract

Both nicotinic cholinergic and NMDA glutaminergic systems are important for memory function. Nicotine has been found repeatedly to significantly improve working memory performance in the radial-arm maze. The NMDA antagonist dizocilpine has been found to impair working memory performance. There is neuropharmacological evidence that these two systems are functionally related. Nicotine is potent at releasing many transmitters including glutamate. The current study was conducted to examine the interaction of nicotinic and NMDA systems within the amygdala with regard to working and reference memory. Rats were trained on a working/reference procedure on a 16-arm radial maze. After acquisition, local infusion cannulae were implanted bilaterally into the amygdala and piriform cortex using stereotaxic techniques. Then 20 min prior to running the rats on the radial-arm maze, they were injected subcutaneously with (-) nicotine ditartrate at doses of 0 and 0.4 mg/kg. Following this, the rats received local infusions of (+) dizocilpine maleate (MK-801) at doses of 0, 2, 6 and 18 microg per side into the lateral amygdala or piriform cortex 10 min prior to running on the radial-arm maze. Each of the eight nicotine and dizocilpine combinations was administered to each rat in a counterbalanced order. After completion of the drug sessions the rats were sacrificed, and using histological methods the cannulae placements were verified. Acute amygdalar infusions of the NMDA glutamate receptor antagonist dizocilpine induced dose-related working and reference memory deficits in the radial-arm maze. Systemic nicotine was not seen to reverse these effects. Dizocilpine infusions into the adjacent piriform cortex did not impair memory function, supporting the specificity of dizocilpine effects in the amygdala. Latency effects were seen with both drugs in both areas. Latencies were decreased with both systemic nicotine and dizocilpine in both the lateral amygdala and the piriform cortex. This study demonstrated the importance of NMDA glutamate systems in the amygdala for appetitively-motivated spatial memory performance.