Circadian rhythms in rat brain neurotransmitter receptors.

In the rat brain there are daily rhythms in the number of alpha- and beta-adrenergic, muscarinic cholinergic, dopamine, opiate, and benzodiazepine receptors. The rhythms are circadian, i.e., with periods of approximately 24 h and endogenously generated. The characteristics of the circadian rhythms change over the year. Ablation of the suprachiasmatic nuclei, believed to act as a biological clock, abolishes the circadian rhythms. In the cerebral cortex the circadian rhythm in norepinephrine-stimulated cyclic AMP production is a biological response to the circadian rhythms in alpha- and beta-adrenergic receptors. The effects on neurotransmitter receptor rhythms of treatments that are antidepressant in humans were studied. Chronic administration of the antidepressant drugs imipramine and clorgyline delays the timing of the peak number of many receptors. Chronic administration of the antidepressant, antimanic drug lithium carbonate delays the timing of the peak number of some receptors and abolishes the rhythms in several others. Twenty-four hours of sleep deprivation is almost without effect on the rhythms. Fluphenazine and lithium, both antimanic in humans, increase the 24-h mean number of most receptors. Circadian receptor rhythms evoking intracellular circadian biological responses may modulate brain neurotransmission, coordinating internal physiological processes, and synchronizing them to environmental events. Alterations in circadian receptor rhythms with chronic psychoactive drug administration may play a role in the therapeutic actions of these drugs.