Individual and combined effects of beta-amyloid1-42, donepezil and haloperidol on long-term potentiation in rat hippocampus
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1
Center of Neurology RAMS, Russia
Donepezil is a potent acetylcholinesterase inhibitor used for the treatment of Alzheimer’s disease (AD). Additional therapeutically relevant target for donepezil is sigma1 receptors (Kato et al., 1999). It is generally believed that beta-amyloid peptides (Abeta) contribute to the pathogenesis of AD. Low concentrations of Abeta were shown to impair long-term potentiation (LTP) in hippocampus (Chen et al., 2000). It was shown in our previous work that donepezil in concentration of 1 microM antagonizes the suppressive action of Abeta1-42 on LTP in rat hippocampal slices. We suppose that sigma1 receptors might be involved into mechanism(s) of this effect of donepezil. The purpose of present study was to determine whether donepezil-induced reversal of LTP impaired by Abeta can be abolished by haloperidol, a potent antagonist of sigma1 receptors (Hayashi & Su, 2008). In the control group, the amplitude of population spikes (PS) 30 min post-tetanus reached 146±11% (n = 10). Neither 1 microM donepezil (n = 6), nor 0,5 microM haloperidol (n = 5) changed LTP significantly. Abeta1-42 (200 nM) markedly suppressed the LTP induction or even caused the depression of PS: the amplitude of PS 30 min post-tetanus was 82 ± 15% (p < .005, n = 7). This suppression of LTP could be markedly prevented when donepezil was co-administered with Abeta: the amplitude of PS 30 min post-tetanus was 136 ± 11% (p < .05, n = 5). Further, we co-administered three substances: Abeta, donepezil and haloperidol, and have found that haloperidol antagonizes the stimulating action of donepezil on LTP: the amplitude of PS 30 min post-tetanus was 92 ± 6% (p < .05, n = 5). Results suggest the involvement of sigma1 receptors into mechanisms of the rescue of hippocampal LTP impaired by Abeta by donepezil. Funding: Supported by grant from Russian Foundation for Basic Research.
Keywords:
AD,
Neuropsychiatry
Conference:
XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011.
Presentation Type:
Poster Presentation
Topic:
Poster Sessions: Neuropsychiatric Applications
Citation:
Solntseva
E and
Kapai
N
(2011). Individual and combined effects of beta-amyloid1-42, donepezil and haloperidol on long-term potentiation in rat hippocampus.
Conference Abstract:
XI International Conference on Cognitive Neuroscience (ICON XI).
doi: 10.3389/conf.fnhum.2011.207.00226
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Received:
21 Nov 2011;
Published Online:
28 Nov 2011.
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Correspondence:
Dr. Elena Solntseva, Center of Neurology RAMS, Moscow, Russia, soln@front.ru