# CHOLINERGIC RECEPTOR CHANGES IN ALZHEIMER MODEL

> **NIH NIH R01** · MONTEFIORE MEDICAL CENTER (BRONX, NY) · 1993 · $95,599

## Abstract

The broad, long-term objectives of this proposal are to evaluate the
extent to which the changes in cholinergic receptor function that have
been described in Alzheimer's disease can be mimicked in an
animal model, to use the model to examine the mechanisms underlying
adaptive changes, and to characterize the resulting alterations in
cholinergic pharmacology.  The hypothesis to be tested is that lesioning
cholinergic inputs to the hippocampus causes changes in cholinergic
receptors and function similar to those in Alzheimer's disease.  This
will be tested in an animal model in which about 50% of hippocampal
cholinergic neurons have been lesioned with the neurotoxin ethylcholine
mustard aziridinium (AF64A).  Specific aims are: 1) Examine whether the
function of presynaptic cholinergic autoreceptors which modulate
acetylcholine release from the surviving cholinergic neurons is altered
in hippocampal slices from AF64A treated rats; 2) Examine whether the
function of one population of postsynaptic cholinergic receptors, those
which modulate norepinephrine release, is altered by lesion of
cholinergic neurons; 3) Determine whether muscarinic receptor numbers and
affinities are altered in lesioned animals, and whether changes in
muscarinic receptor function result from uncoupling from G-proteins; 4)
Determine whether receptor changes can be prevented by chronic
administration of cholinergic agonists from the time of lesioning.  These
findings will provide important information which will aid in developing
new drug treatments for Alzheimer's disease.  The experimental design
compares several functional aspects of muscarinic and nicotinic
cholinergic receptors in hippocampus of normal and AF64A-lesioned rats,
to determine whether these functions are altered by the cholinergic
lesion in the same way as in Alzheimer's disease.  The methods to be used
are: 1) constructing dose-response curves for modulation of the
stimulation evoked release of radioabelled acetylcholine and
norepinephrine from hippocampal slices by muscarinic and nicotinic
agonists, and determining whether these curves are shifted in
AF64A-treated rats; 2) measuring binding of radiolabelled ligands to
muscarinic and nicotinic receptors in hippocampus; 3) assessing coupling
of muscarinic receptors to G-proteins using radioreceptor assays; and 4)
measuring the shift in the dose response curve for modulation of
acetylcholine and norepinephrine release when receptors are uncoupled
with N-ethylmaleimide.

## Key facts

- **NIH application ID:** 3123331
- **Project number:** 5R01AG011384-02
- **Recipient organization:** MONTEFIORE MEDICAL CENTER (BRONX, NY)
- **SAM.gov UEI:** FP1VD1HU5HV7
- **Principal Investigator:** PAMELA E POTTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $95,599
- **Award type:** 5
- **Project period:** 1992-09-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123331

## Citation

> US National Institutes of Health, RePORTER application 3123331, CHOLINERGIC RECEPTOR CHANGES IN ALZHEIMER MODEL (5R01AG011384-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123331. Licensed CC0.

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