Effect of Lithium on Circadian Neurotransmitter Receptor Rhythms

Abstract

Chronic lithium administration significantly changes characteristics of the circadian rhythms in rat brain α- and β-adrenergic, muscarinic acetylcholine, dopamine, opiate, and benzodiazepine receptors. There are changes in the timing of the peak number of receptors (phase-position), in the amplitude of the rhythms, and in the 24-hour mean number of receptors. The circadian rhythm in the number of forebrain α- and β-adrenergic and benzodiazepine receptors is abolished. The phase-position of forebrain acetylcholine and opiate receptors and striatal benzodiazepine receptors is delayed. As the rhythms of the dopamine receptor number and α-melanocyte-stimulating hormone secretion become bimodal, their phase positions are difficult to evaluate. The mean number of forebrain α- and β-adrenergic, acetylcholine, opiate, and striatal benzodiazepine receptors increases. The mean number of forebrain benzodiazepine and striatal dopamine receptors and the mean concentration of α-melanocyte-stimulating hormone decreases. Lithium has profound effects on each of the receptor rhythms measured. Slowing and altering circadian rhythms may contribute to the therapeutic effects of chronic lithium treatment in affective disorders.

Effects of Lithium on the .BETA.-Adrenergic Receptor-Adenylate Cyclase System in Rat Cerebral Cortical Membranes.

“…1). This result is consistent with some previous reports (13)(14)(15), whereas it is inconsistent with others in which no significant change (16)(17)(18)(19)(20) or an increase (21) in densi ties of /3-adrenergic receptors by long-term lithium administration was reported. While the precise cause of this discrepancy is unknown, the difficulty in detecting a relatively small amount of decrease in density of fi-adreno ceptors induced by long-term lithium treat ment was pointed out (15).…”

Effect of Time-of-Day on the Yawning Response to Apomorphine in Normal Subjects

“…In the rat, there is a circadian variation in tyrosine hydroxylase activity, DA turnover [26], DA levels [26,27] and number of DA receptors [28][29][30]. A change in receptor number could explain our present findings of a difference in yawning response depending on time of day of Apo administration.…”

Cortisol Changes in Long-Term Lithium Therapy

“…Halmi et al [1972] demonstrated that in healthy persons the circadian variation of serum cortisol was smaller dur ing lithium administration than when they were receiving a placebo -due to the lower morning cortisol levels while on lithium. Recently, some studies in animals have shown that lithium delayed hormone circadian rhythms [McEachron et al, 1982] and that cholinergic and adren ergic receptor rhythms were also delayed or decreased in their amplitudes by lithium [Kafka et al, 1982;Wehrand Wire-Justice, 1982].…”