A cholinergic role in the mechanism of lithium in mania

G. D. Tollefson, Susan Senogles

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Based on evidence that mania may include an alteration of cholinergic function, we have previously investigated the effects of various monovalent ions on the muscarinic cholinergic receptor from human caudate nucleus utilizing the radio-labeled antagonist (3H)quinuclidinyl benzilate (QNB). In this study we observed that Li+ at 1 mM was unique in its ability to specifically reduce the affinity of 3H-QNB for the muscarinic receptor (increasing the QNB dissociation constant from 35.9 pM to 72.4 pM). The sodium-specific induction of positive cooperativity (n(Hill)) at the muscarinic cholinergic receptor was inhibited in the presence of Li+. Both observations achieved statistical significance at p<0.05. A Li+-related decrease in specific QNB binding sites (B(max)) by 23% (from 2480 to 1900 pmole/g protein) was additionally manifest, albeit only achieving a statistical trend (p<0.10). The exact mode of Li+ action in the management of major affective illnesses remains speculative. The observation that this cation specifically mediates a reduction of muscarinic receptor affinity and number of binding sites within the human caudate suggests further consideration of the association between muscarinic cholinergic activity and mania as it relates to Li+.

Original languageEnglish (US)
Pages (from-to)467-479
Number of pages13
JournalBiological Psychiatry
Volume18
Issue number4
StatePublished - Jan 1 1983

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Muscarinic Receptors
Bipolar Disorder
Lithium
Cholinergic Agents
Quinuclidinyl Benzilate
Cholinergic Receptors
Aptitude
Caudate Nucleus
Radio
Cations
Sodium
Binding Sites
Ions
Proteins
quinuclidinyl benzilate receptor

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

Cite this

A cholinergic role in the mechanism of lithium in mania. / Tollefson, G. D.; Senogles, Susan.

In: Biological Psychiatry, Vol. 18, No. 4, 01.01.1983, p. 467-479.

Research output: Contribution to journalArticle

Tollefson, G. D. ; Senogles, Susan. / A cholinergic role in the mechanism of lithium in mania. In: Biological Psychiatry. 1983 ; Vol. 18, No. 4. pp. 467-479.
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