Cholinergic drug effects and brain muscarinic receptor binding in aged rats

doi:10.1016/0197-4580(84)90067-8

Neurobiology of Aging

Volume 5, Issue 3, Autumn 1984, Pages 227-233

https://doi.org/10.1016/0197-4580(84)90067-8 Get rights and content

Abstract

Muscarinic systems are significantly altered in the brains of laboratory animals and man as a result of normal aging. Cholinergic neurotransmission in cerebral cortex and hippocampus is also severely impaired in a major age-related neurological disorder. Alzheimer's disease. The objective of these studies was to assess specific ³H-quinuclidinyl benzilate (³H-QNB) binding to brain muscarinic receptors in young, adult and senescent Fischer 344 rats, and to relate receptor changes to differences in the pharmacologic actions of cholinergic drugs. Muscarinic receptor density declined with advanced age in the frontal cortex, corpus striatum and hypothalamus, but no age-related changes in receptor affinity were observed. Specific binding of ³H-QNB in hippocampus was not significantly altered. In contrast, the in vivo effects of oxotremorine (hypothermia and antinociception) were markedly enhanced in aged rats, whereas scopolamine-induced locomotor activity was reduced. Hence, senescent rats were more sensitive to the pharmacologic actions of a cholinergic agonist, but less responsive than young rats to a muscarinic antagonist. These seemingly contradictory results of binding experiments and pharmacological studies could be due, in part, to changes in subtypes of brain muscarinic receptors with advanced age. Alternatively, the age-related differences in cholinergic drug effects may reflect a decreased ability of the senescent animal to adapt to changes in its environment.

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Muscarinic receptor number (but not affinity) is decreased, although this is dependent on receptor subtype and brain region (Pedigo et al., 1984; Tayebati et al., 2004). Receptor plasticity is impaired in terms of response to chemicals or pathological insult (Pedigo et al., 1984; Pedigo, 1994; Taylor and Griffith, 1993). Decreased acetylcholine synthesis and release as well as altered post-synaptic signal transduction and neuronal responsivity have also been reported (Decker, 1987).
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Cholinergic drug effects and brain muscarinic receptor binding in aged rats

Abstract

Behav Brain Res

J Neurol Sci

Anal Biochem

Neurobiol Aging

J Biol Chem

Biochem Biophys Res Commun

Brain Res

Neurobiol Aging

Life Sci

Prog Neuropsychopharmacol

Int J Neuropharmacol

Life Sci

J Neurol Sci

Life Sci

Brain Res

Neurobiol Aging

Biochemical evidence of selective nerve cell changes in the normal aging human and rat brain

J Neurochem

Behavioral and pharmacological studies using animal models of aging: implications for studying and treating dementia of Alzheimer's type

The binding of agonists to brain muscarinic receptors

Mol Pharmacol

Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease

J Neurochem