Lithium and melatonin in pigmented eye rats: Effects of dose and time of day

Abstract

Lithium has been suggested to exert sane of its theraputic effects by modifying the function of the retinal-hypothalamic pineal pathway that is essential for the chronobiology of an organism (Seggie et al., 1983). Previous work was done in Wistar rats, an Albino species which lacks the enzyme for synthesis of eye pigment. This pigment is important in the regulation of light cued rhythms. The present project investigated effects of lithium in a pigmented eye strain. Adult male Long Evans rats were maintained individually on a 12 hour light/12 hour dark schedule with free access to water and one of three diets: (1) normal laboratory chow; (2) a low lithium diet: lab chow supplemented with 30 mM/kg of lithium chloride and (3) a high lithium diet: lab chow supplemented with 50 mM/kg of lithium chloride. Body weight and water intake were measured after six weeks on the diets. In Experiment I, separate groups of rats were sacrificed by rapid decapitation every 4 hours in the light/dark cycle. In Experiment II, animals were sacrificed every 90 min. between 12:00 and 20:00 hours during the dark cycle. Blood and pineal glands were collected for lithium determination and assay of melatonin by RIA. In Experiment I, plasma lithium levels were 0.35 ± 0.01 and 0.57 ± 0.02 mmEq/1 for the low and high diets. Serum and pineal melatonin evidenced the expected diurnal rhythms. The diets had no effect on these parameters except at 14:00 hours. At this time, two hours after lights out, the high diet but not the low diet group evidenced significantly lower serum melatonin levels than the control group (F = 4.91, df 2, 10, p < .05 for means of 14.0 ± 3.9 pg/ml vs 34.7 ± 5.6 pg/ml). In Experiment II plasma lithium levels were 0.39 ± 0.01 and 0.62 ± 0.01 mEq/1 for the low and high diets. Pineal and serum melatonin rhythms were again as expected and the diets had no effect except at 13:30 hours. At this time pineal melatonin content was significantly reduced by both diets. Control values were 2100 ± 133 pg/pineal, low diet 1222 ± 299 pg/pineal and high diet 905 ± 251 pg/pineal. (Control vs low F = 6.89, df 1, 8, p < .05; control vs high F = 15.5 df 1, 9, p < .01). Body weight was significantly reduced by both diets. Water intake was increased by the high diet and not affected by the low diet. In view of the consistency of time for the present significant findings, it is suggested that lithium is exerting a subtle and short-lived effect on pineal melatonin levels during the period shortly after the switch to darkness and maybe influencing the characteristics of the “turn-on” effects of this important timing cue. In Albino rats, diet supplemented with 50 mM/Kg of lithium chloride affected the pattern of serum melatonin levels between 14:00 and 22:00 hours (Seggie et al., 1983). Thus, a strain effect of lithium cannot be ruled out.