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Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors
Barnes CA, Meltzer J, Houston F, Orr G, McGann K, Wenk GL.. Neuroscience, 2000-01-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
The function of the cholinergic system is known to change during normal aging and in pathological conditions such as Alzheimer's disease. The present study was designed to assess, within the same group of old animals, the behavioral, electrophysiological and neurochemical effects of chronic treatment with agents that increase the function of the cholinergic system through both muscarinic and nicotinic mechanisms. Doses were determined that produced 60% cholinesterase inhibition by donepezil and galantamine for the old rats. This was chosen to be analogous to therapeutic levels achieved for treatment of human Alzheimer's disease patients with these agents. Because of the well-known age-related changes in spatial memory and hippocampal synaptic plasticity, spatial working memory in the radial eight-arm maze and hippocampal long-term potentiation induction and decay, as well as nicotinic receptor density and affinity, were measured in old rats implanted with minipumps that delivered donepezil, galantamine or saline. There was no effect of drug treatment on baseline synaptic transmission or on the threshold or magnitude of long-term potentiation induction. Both drug treatment groups, however, showed significantly extended long-term potentiation decay times at the perforant path-granule cell synapse over the saline control animals, as measured during the week following induction. Both drugs also elevated the number of nicotinic receptors within the hippocampus and neocortex. This is the first demonstration of cholinergic modulation of synaptic plasticity over the time-course of days. Furthermore, the durability of long-term potentiation was significantly, positively correlated with nicotinic receptor binding in the hippocampus. Chronic treatment with donepezil or galantamine had no significant effect on a well-learned spatial working memory task on the radial maze. These data suggest that the therapeutic doses of cholinesterase inhibitors used to treat patients with Alzheimer's disease may have effects on neurophysiology and neurochemistry that are close to the threshold for producing detectable behavioral improvements.
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APA 7th
Barnes, C. A., Meltzer, J., Houston, F., Orr, G., McGann, K., & Wenk, G. L. (2000). Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors. Neuroscience. https://doi.org/10.1016/s0306-4522(00)00180-9
Vancouver
Barnes CA, Meltzer J, Houston F, Orr G, McGann K, Wenk GL. Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors. Neuroscience. 2000. doi:10.1016/s0306-4522(00)00180-9. PMID: 10924948.
BibTeX
@article{barnes2000-10924948,
author = {Barnes, C. A. and Meltzer, J. and Houston, F. and Orr, G. and McGann, K. and Wenk, G. L.},
title = {{Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors}},
journal = {Neuroscience},
year = {2000},
doi = {10.1016/s0306-4522(00)00180-9},
pmid = {10924948},
url = {https://doi.org/10.1016/s0306-4522(00)00180-9}
}
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Key findings
- Both drug treatment groups, however, showed significantly extended long-term potentiation decay times at the perforant path-granule cell synapse over the saline control animals, as measured during the week following induction.
- Furthermore, the durability of long-term potentiation was significantly, positively correlated with nicotinic receptor binding in the hippocampus.
- Chronic treatment with donepezil or galantamine had no significant effect on a well-learned spatial working memory task on the radial maze.
- These data suggest that the therapeutic doses of cholinesterase inhibitors used to treat patients with Alzheimer's disease may have effects on neurophysiology and neurochemistry that are close to the threshold for producing detectable behavioral improvements.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2000 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “rats”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10924948) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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