Beta-amyloid blocks high frequency stimulation induced LTP but not nicotine enhanced LTP

Nicotine has been postulated to be a possible neuroprotective agent in Alzheimer's Disease (AD). In the present studies, the effect of beta-amyloid (Aβ) was investigated on the nicotine enhancement of high-frequency-induced LTP. Perfusion of nicotine substantially enhanced HFS-induced LTP in both rat and mouse dentate gyrus. The enhancing action of nicotine was mediated via α7 nAChRs as it was absent in mice null for α7 nAChR. Aβ strongly inhibited the induction of LTP in control animals, with LTP being completely inhibited at 1 h post-HFS. Although Aβ also inhibited LTP in the presence of nicotine, the extent of the inhibition of LTP in nicotine perfused slices was similar to that in control, resulting in substantial LTP remaining in the presence of Aβ in the nicotine perfused slices. The nicotine enhanced LTP and the LTP remaining in the presence of Aβ and nicotine, although not the control LTP was dependent on activation of PKA. Chronic nicotine treatment also enhanced HFS-LTP recorded in acute slices taken from the nicotine-treated animals, and such LTP was only partially inhibited by Aβ. We postulate that nicotine-enhanced LTP has certain different mechanisms to that of control LTP which results in a resistance to inhibition by Aβ.