The effect of lithium on noradrenaline-induced cyclic AMP accumulation in rat brain: inhibition after chronic treatment and absence of supersensitivity

RP Ebstein, M Hermoni and RH Belmaker

Lithium (Li) has been reported to inhibit numerous adenylate cyclases, but often these reports used clinically toxic concentrations of Li and their relevance to a theory of Li action was questionable. The present report demonstrated Li inhibition beginning at 2 mM of the norepinephrine (NE)-induced cyclic AMP accumulation in a resuspended P2 pellet containing intact synaptosomes and in slices from rat cortex. The inhibition is demonstrable with isoproterenol as well and in the presence of a phosphodiesterase inhibitor. In cortical slices removed from rats treated for 21 days with therapeutically equivalent Li serum levels, NE-induced cyclic AMP accumulation is inhibited by over 70%. After cessation of 21 or 42 days of Li treatment, an enhancement of cyclic AMP accumulation to NE is not demonstrable. Rubidium and cesium do not inhibit NE-induced cyclic AMP accumulation. These ions cause an increase in basal cyclic AMP accumulation in the absence of NE, as does Li to a lesser degree. The effect of Li to inhibit NE-induced cyclic AMP accumulation is therefore specific to the Li ion, occurs at therapeutically equivalent concentrations, continues after chronic treatment and does not cause a compensatory supersensivity in the manner of the NE-receptor blocking drugs.

Volume 213, Issue 1, pp. 161-167, 04/01/1980
Copyright © 1980 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				N. B. Karkanias and R. L. Papke Subtype-Specific Effects of Lithium on Glutamate Receptor Function J Neurophysiol, April 1, 1999; 81(4): 1506 - 1512. [Abstract] [Full Text] [PDF]