Chronic treatment with choline or scopolamine indicates the presence of muscarinic cholinergic receptor plasticity in the frontal cortex of young but not of aged mice

H, Pilch; Müller, Wernér E.G.

doi:10.1007/bf01259408

Cited by 23 publications

(3 citation statements)

References 15 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Pilch and Muller (1988) have demonstrated that muscarinic receptor plasticity appears to be lost in aged animals. Therefore, attempts to ameliorate memory impairments associated with the cholinergic deficit in these structures in Alzheimer's disease (see Bartus et al, 1982) by increasing in vivo ACh release with muscarinic-Mvl, antagonists may be a difficult endeavor.…”

Section: Discussionmentioning

confidence: 99%

Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites

et al. 1990

View full text Add to dashboard Cite

The main objective of the present work was to determine whether the regulation of ACh release by nicotinic and muscarinic autoreceptors is compromised in the aged rat brain. For this, the effects of the nicotinic agonist N-methylcarbamylcholine (MCC) and the muscarinic-M2 antagonist AF-DX 116 on ACh release from brain slices of young (3-month-old), adult (9-month-old), and aged (27-month-old) rats were tested. The ability of MCC to enhance spontaneous ACh release in hippocampal, cerebral cortical, and cerebellar slices was only modestly altered with age. In contrast, the sensitivity of muscarinic autoreceptors in the aged hippocampus and cerebral cortex, but not the striatum, to blockade by the muscarinic-M2 antagonist AF-DX 116 was severely attenuated. To assess whether the age-related changes in cholinergic autoreceptor function may be due to deficits in presynaptic cholinergic markers, we tested whether choline acetyltransferase (ChAT) activity, basal and evoked ACh release, and nicotinic and muscarinic binding sites are altered in the aged rats. ChAT activity in forebrain regions was decreased in the aged compared to the young and mature adult rats. Furthermore, the potassium-evoked, but not the spontaneous, release of ACh was markedly depressed in striatal, hippocampal, and cortical slices of aged rats. The densities of nicotinic and muscarinic-M2 binding sites, assessed using 3H-MCC and 3H-AF-DX 116 as selective ligands, respectively, were markedly reduced in homogenates of the striatum, hippocampus, cerebral cortex, and thalamus of aged rats. In contrast, muscarinic-M1 sites, selectively labeled with 3H-pirenzepine, were not affected. Therefore, it appears that age-related decrements in ChAT activity and in muscarinic-M2, but not nicotinic, binding sites in the rat brain are reflected in a decreased function of muscarinic-M2 autoreceptors. However, the positive correlation between loss of ChAT activity, decreased muscarinic-M2 binding sites, and impaired muscarinic autoreceptor function is clearly tissue dependent.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites

et al. 1990

View full text Add to dashboard Cite

show abstract

“…Chronic administration of haloperidol upregulates the dopaminergic receptors in the frontal cortex (MacLennan et al, 1988). Similarly, chronic biperiden administration must upregulate muscarinic receptors in the frontal cortex, as chronic administration of scopolamine has been shown to upregulate muscarinic receptors in the frontal cortex (Pietrzak et al, 1989;Pilch Fig. 3.…”

Section: Discussionmentioning

confidence: 99%

Administration of haloperidol with biperiden reduces mRNAs related to the ubiquitin-proteasome system in mice

Iwata

Morioka

Iwabuchi

et al. 2005

Synapse

View full text Add to dashboard Cite

In order to find molecules affected by administration of an antipsychotic drug with an antimuscarinic drug, which is a common prescription used to prevent extrapyramidal adverse effects caused by the antipsychotic drugs, gene expression profiling in the frontal cortex was studied in mice. After 14 days of administration with 2 mg/kg haloperidol, a typical antipsychotic drug, and 2 mg/kg biperiden, a high-affinity antagonist for muscarinic receptors in the brain, approximately 500 mRNAs related to synaptic function were investigated. The levels of the mRNAs related to the ubiquitin-related systems were significantly reduced after the combined administration. However, the separate administration of either haloperidol or biperiden had little effect on the levels of the mRNAs. This result suggests that coadministration of haloperidol and biperiden specifically affects the ubiquitin-related system.

show abstract

“…Electrophysiological experiments in the hippocampus of old rats showed impairment in neuronal response to local application of ACh (but not of glutamate) without consistent changes in receptor number (1). Chronic treatment with the cholinergic agonist or antagonist induced changes in receptor number (down-and up-regulation, respectively) in the frontal cortex ofyoung but not aged mice (34). On the other hand, modifications in receptor structure could be secondary to the changes in membrane properties reported in aging.…”

mentioning

confidence: 90%

Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys.

Vannucchi

Goldman‐Rakic²

1991

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In vitro autoradiography on tissue sections and receptor assay in cortical membrane homogenates revealed that pirenuzepine h-affinity muscarink sites (Ml) decrease in affinity in the prefrontal cortex and in other cortical areas of aged rhesus monkey (Macaca miudta). Carbachol competition experiments detected only a single, low-affinity da of sites in old monkeys, while two classes of sites (low and hh affity) were observed in young adults. The change in affinity in the aged monkeys is not accomaed by a decrease in the density ofthese sites and, further, the age-related decline in the affinity ofthe Ml site is reversible. In the presence of Mg2e, the Ml muarnic receptors in the aged monkeys were capable of forming carbachol high-affinity sites. These results provide evidence for agedependent funtional changes in receptor activity in cerebral cortex and indicate that these receptors maintain a degree of plasticity that could be a strategc target for research aimed at treatment of memory disorders in aged humans.Memory decline during aging has been extensively documented in rodents (1, 2), nonhuman primates (3, 4), and humans (5). Although the aging process seems to impinge on several neurotransmitter systems, special emphasis has been placed on the role of the cortical cholinergic innervation in geriatric memory dysfunction (6). Studies in rodents have shown a consistent decline in cortical acetylcholine (ACh) synthesis and release during aging (7-9), although little or no change occurs in cortical choline acetyltransferase activity (1,8,6,10). Further, the cholinergic basal forebrain neurons that project to the cortex undergo an age-related decrease in size though their number is apparently not diminished (11).In the present study we have examined the status of the Ml muscarinic cholinergic receptor in aged rhesus monkey, a species that exhibits behavioral impairment and cortical pathological changes remarkably similar to those observed in elderly humans (4,6,12). Ml sites are present in high concentration in the primate neocortex (13,14) and are involved in cortical cholinergic excitation (15). However, little is known about changes in these cortical receptors with age. In aged rats, there have been conflicting reports of decrease (16) or no change (17) in binding-site density. Only two recent studies have examined the status of ACh receptors in monkey cortex during aging, and both found a decrease of nicotinic and muscarinic receptors, mainly in temporal (18,19) and parahippocampal (18) cortex. Neither study found any significant decreases in the affinity of binding sites in aged monkey cortex.In the present study we confirm that the number of Ml sites does not change with age but we provide evidence for changes in the molecular structure of the cortical receptor or of the coupled effector systems able to alter the affinity of these sites. To obtain this evidence, we studied the binding of the highly selective compound pirenzepine (PZ) (20) to the Ml sites in nine distinct areas of monkey cortex both i...

show abstract

Chronic treatment with choline or scopolamine indicates the presence of muscarinic cholinergic receptor plasticity in the frontal cortex of young but not of aged mice

Cited by 23 publications

References 15 publications

Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites

Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites

Administration of haloperidol with biperiden reduces mRNAs related to the ubiquitin-proteasome system in mice

Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys.

Contact Info

Product

Resources

About