Abstract
The effects of lithium on several brain energy metabolites were investigated in rats. Lithium was administered by three alternative routes: 1) in food, 2) via IP injection, or 3) intracisternally via the suboccipital route. Lithium given in food induced permanent changes, mainly in glycolytic processes and in glycogen content. Lithium injected IP induced, in addition, several changes which depended on the increase in brain lithium concentration following injection of lithium. These changes in brain metabolites disappeared as brain lithium concentration stabilized. Intracisternal injection of lithium produced brain lithium concentrations between 1 and 2 mmoles/kg wet wt., with a mean of about 1.6 mmoles/kg wet wt. Lithium concentrations below about 1.6 mmoles/kg wet wt. induced changes in brain metabolites which were similar to the changes seen after IP injection of lithium. Lithium concentrations above about 1.6 mmoles/kg wet wt. induced changes in several brain metabolites which were at variance with the changes induced by lower lithium concentrations. These changes were in many respects similar to changes in brain metabolites seen in rats exposed to convulsive treatment.
It is hypothesized that such metabolic changes during lithium treatment, in discrete areas of the brain with higher concentration of lithium, e.g., hypothalamus, might be related to the prophylactic effect of lithium treatment in man.
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References
Arruda JAL, Roseman MK, Sehy JT, Nascimento L, Batlle D, Kurtzman NA (1980) Effect of lithium administration on distal nephron function. Mineral Electrolyte Metab 4:81–88
Bakay L (1952) Studies on the blood brain barrier with radioactive phosphorus. Hypophysis and hypothalamus in man. Arch Neurol 68:629–640
Edelfors S (1975) Distribution of sodium, potassium and lithium in the brain of lithium-treated rats. Acta Pharmacol Toxicol 37:387–392
Galla JN, Forrest JN, Hecht B, Kashgarian M, Hayslett JP (1975) Effect of lithium on water and electrolyte metabolism. Yale J Biol Med 48:305–314
Hofer HW, Pette D (1968) Actions and interactions of substrates and effectors of phosphofructokinase from rabbit skeletal muscle. Hoppe Seylers Z Physiol Chem 349:1378–1392
Knapp S, Mandell AJ (1975) Effects of lithium chloride on parameters of biosynthetic capacity for 5-hydroxytryptamine in rat brain. J Pharmacol Exp Ther 193:812–823
Lowry OH, Passoneau JV (1972) A flexible system of enzymatic analysis. Academic Press, New York
Mellerup ET, Thomsen HG, Bjørum N, Rafaelsen OJ (1972) Lithium, weight gain, and serum insulin in manic-depressive patients. Acta Psychiatr Scand 48:332–336
Mellerup ET, Lauritzen BJ, Dam H, Rafaelsen OJ (1976) Lithium effects on diurnal rhythm of calcium, magnesium, and phosphate metabolism in manic-melancholic disorders. Acta Psychiatr Scand 53: 360–370
Mellerup ET, Dam H, Plenge P, Rafaelsen OJ (1981) Lithium effects on citrate metabolism in humans and rats. Psychopharmacology 73:75–76
Mukherjee BP, Bailey PT, Pradhan SN (1976) Temporal and regional differences in brain concentrations of lithium in rats. Psychopharmacology 48:119–121
Nordenberg J, Kaplansky M, Beitner R (1980) Influence of lithium on glucose 1,6-diphosphate levels in muscle of normal and dystrophic mice. Ir J Med Sci 8:880
Ottosson J-O (1974) Systemic biochemical effects of ECT. In: Fink M, Kety S, McGaugh J, Williams TA (eds) Psychobiology of convulsive therapy. Winston/Wiley, New York, pp 209–220
Peselow ED, Dunnar DL, Fieve RR, Lautin A (1980) Lithium carbonate and weight gain. J Affective Disorders 2:303–310
Plenge P, Mellerup ET, Rafaelsen OJ (1973) Weight gain in lithium-treated rats. Int Pharmacopsychiatry 153:234–238
Plenge P (1976) Acute lithium effects on rat brain glucose metabolism—in vivo. Int Pharmacopsychiatry 11:84–92
Plenge P (1978) Lithium effects on rat brain glucose metabolism in longterm lithium-treated rats studied in vivo. Psychopharmacology 58:317–322
Plenge P, Mellerup ET, Nørgaard T (1981) Functional and structural rat kidney changes caused by peroral or parenteral lithium treatment. Acta Psychiatr Scand 63:303–313
Plenge P, Rafaelsen OJ (in press) Lithium effects on calcium, magnesium and phosphate in man: Effects on Balance, bone mineral content, faecal and urinary excretion. Acta Psychiatr Scand
Roscoe JM, Goldstein MB, Halperin ML, Wilson DR, Stinebaugh BJ (1976) Lithium-induced impairment of urine acidification. Kidney Int 9:344–350
Rose IA, Warms JVB, Kosow DP (1974) Specificity for glucose-6-P inhibition site of hexokinase. Arch Biochem Biophys 164:729–734
Rose IA, Warms JVB, Wong LJ (1977) Inhibitors of glucose 1,6-biphosphate synthase. J Biol Chem 252:4262–4268
Rose IA, Warms JVB (1980) Lithium action on glucose uptake in brain: Role of glucose-1,6-P2 as a regulator of hexokinase. Biochem Biophys Res Commun 92:1030–1036
Siesjö BK (1978) Brain energy metabolism. John Wiley and Sons, Ltd., Chichester New York Brisbane Toronto, pp 345–379
Stefanini E, Argiolas A, Gessa G, Fadda F (1976) Effect of lithium on dopamine uptake by brain synaptosomes. J Neurochem 27:1237–1239
Swann AC, Heninger GR, Roth RH, Maas JW (1981) Differential effects of short and long term lithium on tryptophan uptake and serotonergic function in cat brain. Life Sci 28:347–354
Thomsen K (1973) The effect of sodium chloride on kidney function in rats with lithium intoxication. Acta Pharmacol Toxicol 33:92–102
Vendsborg PB, Bech P, Rafaelsen OJ (1976) Lithium treatment and weight gain. Acta Psychiatr Scand 53:139–147
Vendsborg PB (1979) Lithium treatment and glucose tolerance in manic-melancholic patients. Acta Psychiatr Scand 59:306–316
Watanabe H, Passoneau JV (1973) Factors affecting the turnover of cerebral glycogen and limit dextrin in vivo. J Neurochem 20:1543–1554
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Plenge, P. Lithium effects on rat brain glucose metabolism in vivo. Effects after administration of lithium by various routes. Psychopharmacology 77, 348–355 (1982). https://doi.org/10.1007/BF00432769
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DOI: https://doi.org/10.1007/BF00432769