In vivo and in vitro studies on the regulation of cholinergic neurotransmission in striatum, hippocampus and cortex of aged rats

Silvana Consolo, Jian Xin Wang, Francesco Fiorentini, Annamaria Vezzani, Herbert Ladinsky

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Abstract

Young (3 months) and senescent (23 months) rats were challenged with oxotremorine both in vivo, to determine its effects on acetylcholine content in hemispheric regions, and in vitro, to assess its action on K+-evoked release of ACh from brain synaptosomes. The drug failed to inhibit KCl-induced [3H]ACh release from the P2 fraction of striatal and hippocampal homogenates of the senescent animals, whereas it was less efficient in increasing striatal ACh content. In contrast, oxotremorine was still able to stimulate an increase in ACh in the hippocampus and cerebral cortex of the aged rats to the same extent as it did in the young ones. The [3H]ACh output from striatal synaptosomes was lower in old rats with respect to young ones at low KCl depolarizing concentrations but was equal in the two groups at a high depolarizing concentration. In the hippocampus of the senescent rats, the release was significanly lower at each concentration of KCl used, resulting in a parallel downward-shift in the concentration-release plot. We also measured cholinergic muscarinic receptor binding in rat hemispheric regions using the radioligand [3H]dexetemide, a classical non-selective muscarinic receptor antagonist. It was found, in conformity with some of the literature, that receptor binding was decreased by about 32% in striatum of aged female rats as compared to younger rats. Changes were not observed in cortex and hippocampus. Analysis of the binding data indicated that the observed decrease in specific ligand binding was due to a decrease in the number of binding sites without a change in affinity. The results favor, once again, the cholinergic hypothesis for geriatric dysfunction. The possibility that the functional state of the cholinergic neuron depends also on a balance between the cholinergic system and other neurotransmitters known to regulate cholinergic activity is discussed.

Original languageEnglish
Pages (from-to)212-218
Number of pages7
JournalBrain Research
Volume374
Issue number2
DOIs
Publication statusPublished - May 28 1986

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Keywords

  • acetylcholine release
  • aged rat
  • cortex
  • hippocampus
  • muscarinic receptor
  • oxotremorine
  • striatum

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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