Psychopharmacologia

, Volume 38, Issue 2, pp 145–150 | Cite as

The effects of lithium and physostigmine on rat brain acetylcholinesterase activity

  • Lance L. Simpson
Laboratory Studies

Abstract

The anti-cholinesterase activity of lithium and physostigmine have been investigated. The purpose of the study was two-fold: 1. to determine whether lithium could inhibit acetylcholinesterase, and 2. to determine whether repeated injections of physostigmine, a known cholinesterase inhibitor, could result in tolerance. It was found that lithium had no anti-cholinesterase activity in vivo (100 or 200 mg/kg LiCl), and slight anti-cholinesterase activity in vitro. The latter effect was evident only under markedly unphysiological conditions, i.e., concentrated lithium (10−2−10−1 M) and dilute acetylcholinesterase (1∶10000 dilution; w∶v). It was also found that repeated injections of physostigmine (0.75 mg/kg) did not result in tolerance to the anti-cholinesterase effects of the drug. A single challenge dose of physostigmine (0.75 mg/kg, in vivo) or a series of concentrations of physostigmine (10−8−10−5 M, in vitro) resulted in similar inhibition of AChE from animals which had or had not received a 5 day regimen of repeated physostigmine injections. The relationship of these findings to the treatment of mania is discussed.

Key words

Acetylcholinesterase Lithium Physostigmine Rat Brain 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Bibliography

  1. Carroll, B. J., Frazer, A., Schless, A., Mendels, J.: Cholinergic reversal of manic symptoms. Lancet 1973I, 427–428Google Scholar
  2. Ellman, G. L., Courtney, K. D., Andres, V., Jr., Featherstone, R. M.: A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7, 88–95 (1961)Google Scholar
  3. Forn, J., Valdecasas, F. G.: Effects of lithium on brain adenyl oyclase activity. Biochem. Pharmacol. 20, 2773–2779 (1971)Google Scholar
  4. Janowsky, D. S., El-Yousef, M. K., Davis, J. M., Hubbard, B., Sekerke, H. J.: Cholinergic reversal of manic symptoms. Lancet 1972aI, 1236–1237Google Scholar
  5. Janowsky, D. S., El-Yousef, M. K., Davis, J. M., Sekerke, H. J.: A cholinergic-adrenergic hypothesis of mania and depression. Lancet 1972bII, 632–635Google Scholar
  6. Modestin, J., Hunger, J., Schwartz, R. B.: über die depressogene Wirkung von Physostigmin. Arch. Psychiat. Nervenkr. 218, 67–77 (1973)Google Scholar
  7. Schildkraut, J. J.: Neuropharmacology of the affective disorders. Ann. Rev. Pharmacol. 13, 427–454 (1973)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • Lance L. Simpson
    • 1
  1. 1.Departments of Pharmacology and of Psychiatry, College of Physicians and SurgeonsColumbia UniversityNew York City

Personalised recommendations