Hamaue N, Yamazaki Y, Ohmori H, Sumikawa K (2001) Nicotine enhances N-methyl-D-aspartate receptor responses and facilitates long-term potentiation in the hippocampus from rats with cholinergic lesions. Neuroscience 2001 Abstracts 376.5. Society for Neuroscience, San Diego, CA.
Summary: Nicotine reverses cognitive impairments caused by lesion of the cholinergic system and improves performance of Alzheimer’s patients. The mechanisms underlying these effects of nicotine, however, are unknown. Because nicotine facilitates the induction of N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) in the hippocampal CA1 region, we examined whether nicotine enhances NMDAR responses and facilitates LTP induction in the hippocampus from rats with cholinergic lesions. Selective cholinergic denervation of rat hippocampus was performed by the immunotoxin 192 IgG-saporin. We then recorded burst NMDAR responses in hippocampal slices prepared from 192-IgG-saporin-treated rats and found that nicotine (1 μM) enhanced burst NMDAR responses. When GABAergic transmission was completely blocked by picrotoxin, nicotine had no effect on burst NMDAR responses. We also monitored the induction of LTP in 192-IgG-saporin-treated hippocampi and found that a weak tetanus (20 pulses at 100 Hz), which induced LTP in PBS-treated hippocampi, failed to induced LTP. However, in the presence of nicotine (1 μM), a same weak tetanus induced LTP in 192-IgG-saporin-treated hippocampi. Our results suggest that nicotine potentiates NMDAR responses by disinhibition of pyramidal cells and facilitates LTP induction in the hippocampus from animals with cholinergic lesions. The observed nicotine effects may represent the cellular mechanism underlying the compensatory action of nicotine in the presence of cholinergic deficits.
Related Products: 192-IgG-SAP (Cat. #IT-01)