Effect of chronic lithium treatment on rat pineal rhythms: N-acetyltransferase, N-acetylserotonin and melatonin.

Chronic lithium treatment in rats suppressed the peak activity of pineal N-acetyltransferase as well as the maximal concentrations of pineal N-acetylserotonin and melatonin which occur during the dark phase of the light/dark cycle. These changes were not related to changes in the precursor indoles tryptophan, 5-hydroxytryptophan and serotonin, which were unaltered by lithium treatment. The change in N-acetyltransferase activity appears in part to be due to a decreased Vmax of the enzyme, as assessed using tryptamine as the substrate. Lithium also suppressed pineal activity during the light phase of the diurnal lighting cycle as indicated by a markedly reduced cyclic AMP response to L-isoproterenol. In addition, lithium treatment elicited a 1- to 3-hr delay in peak pineal N-acetyltransferase activity. These effects may result from a lithium-induced desensitization of pineal beta adrenergic receptors, from a direct effect of the ion on the suprachiasmatic nucleus and/or from an action on a site distal to this hypothalamus nucleus.