Circadian rhythms of TRH-like peptide levels in rat brain.

This is the first report of diurnal variations in the levels of thyrotropin-releasing hormone-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) in brain regions involved in mood regulation. These peptides have neuroprotective and antidepressant-like properties that may help stabilize chronobiologic systems that are often abnormal in neuropsychiatric disease. We hypothesized that diurnal fluctuations in the levels of these neuropeptides are components of the chronobiologic regulation of autonomic, behavioral and emotional states. Optimal use of these potentially therapeutic agents will benefit from an understanding of their response to, and effect on, normal vegetative, activity and sleep patterns, and the corresponding disordered patterns of mental illness. For these reasons, 16 male, 200 g, Sprague-Dawley rats were maintained for 4 weeks in a stable 12 h lights on, 12 h lights off photoperiod. Levels of TRH and TRH-like peptides were measured at 3.0 h, 10.5 h, 13.5 h and 21.0 h, where the subjective midnight was 0.0 h, by a combination of HPLC and RIA. Highly significant changes in TRH-like peptide levels were observed in the striatum, posterior cingulate, cerebellum, pyriform cortex, nucleus accumbens and medulla oblongata. TRH-like peptide levels, in general, were highly correlated with changes in TRH concentration, within and between brain regions, and may be colocalized in large glutamatergic neurons innervating the rat limbic system. We conclude that TRH-like peptides may be important components of chronobiologic systems involved in maintaining autonomic, behavioral and mood equilibria.