Chronic lithium treatment and twenty-four hour rhythm of serum prolactin, growth hormone and melatonin in rats

Abstract

This study was undertaken to extend the observations that lithium chloride has the ability to phase shift the 24-hour pattern of a large number of physiological parameters relative to the environmental lighting cycle. Adult male Wistar rats were housed individually in a temperature and sound controlled environment under a lighting schedule of 12 hours dark/12 hours light. Six point 24-hour maps were generated by taking measurements every four hours throughout 24 hours on separate groups of rats maintained for six weeks on ad lib water and one of three diets: 1) normal lab chow, 2) lab chow supplemented with 50 mM/kg of lithium chloride, 3) lab chow supplemented with 50 mM/kg of sodium chloride to control for the effects of a possible salt load. Variables measured included plasma and red blood cell lithium and sodium concentrations, serum prolactin, growth hormone and melatonin. Plasma lithium levels were 0.7–1.0 mEq/L. Plasma, but not red blood cell lithium levels deomonstrated a 24-hour rhythm with higher levels following the normal feeding period. Serum and red blood cell sodium levels did not differ among the diets and showed no 24-hour variation. The sodium diet had no significant effects on any of the variables measured. The 24-hour pattern of prolactin was not significantly affected by the diets, while growth hormone and melatonin levels differed in animals on the lithium diet. During the light hours when growth hormone levels are normally falling and melatonin levels are barely detectable, there were no differences on these measurements among the diets. However. during the dark hours when growth hormone and melatonin normally evidence a rise that peaks near the end of the dark phase, lithium fed animals evidence low unchanging levels of growth hormone, while melatonin levels reached peak values in the middle of the dark phase, four hours prior to the controls. The delay in peak values for growth hormone levels is in agreement with the pattern of phase shifting effects observed for many other physiological variables following lithium treatment, namely, a delay or shift to the right. However, the shifting of the melatonin peak to an earlier time In the 24-hour cycle is a unique finding. In rats, serum melatonin comes exclusively from the pineal. In view of the importance of this gland in biological rhythms, the unique shift to the left for melatonin following lithium treatment has important implications for the mechanisms, whereby lithium exerts its rhythm altering effects on biological systems.