Effects of Treatment with Chromium Picolinate on Peripheral Amino Acid Availability and Brain Monoamine Function in the Rat

Elemental chromium (Cr) is an essential micronutrient. It is required for optimal insulin activity and normal carbohydrate and lipid metabolism. Tri-valent chromium (Cr³⁺) is recommended for the treatment of diabetes and obesity. There is evidence that Cr³⁺ may have antidepressant properties, possibly by enhancement of monoamine function through its ability to increase amino acid transport to the brain. The aim of the present study was to investigate further the possible effects of Cr³⁺ treatment on peripheral amino acid availability and brain monoamine function in the rat. We undertook three studies in rats. The first was a time-course study in which animals were administered single doses of 50 mg/kg of Cr³⁺ picolinate and the second a dose-response study in which animals were given either 20 or 50 mg/kg Cr³⁺ picolinate versus vehicle alone via the intra-peritoneal route. In the third, animals were fed a diet containing Cr³⁺ picolinate (100 mg/kg) or a similar control diet for two weeks and were then sacrificed. Blood was sampled and brains were removed for later analysis. Results from the Cr³⁺ time-course study defined an optimal time for sampling of two hours after dosing. Results from the second study showed dose-related responses to Cr³⁺ treatment for a number of measured biochemical parameters including serum corticosterone.

In the sub-chronic treatment study Cr³⁺ significantly increased serum free tryptophan (TRP), non-esterified free fatty acids (NEFFAs), corticosterone, together with brain TRP, serotonin (5-hydroxytryptamine, 5-HT), noradrenaline (NA) and pineal melatonin. From other studies in our laboratory we have shown that Cr³⁺ treatment can modify brain 5-HT function, perhaps by altering the sensitivity of central 5-HT_2A receptors. The peripheral effect of Cr³⁺ picolinate treatments and their consequential central effect on increased serotonergic and noradrenergic function may suggest that Cr³⁺ could have some antidepressant-like actions. Future studies to confirm this are to be done.

Key words

Cr³⁺ picolinate - TRP - 5-HT - NA - Melatonin - NEFFAs - corticosterone

References

• 1 Anderson R A. Chromium, glucose tolerance, diabetes and lipid metabolism.  J Advancement Med. 1995;  8 37-39
• 2 Anderson R A, Bryden N A, Polansky M M. Lack of toxicity of chromium chloride and chromium picolinate in rats.  J Amm Coll Nutrition. 1997;  16(3) 273-279
• 3 Attenburrow M -J, Odontiadis J, Murray B J, Cowen P J, Franklin M. Chromium treatment decreases the sensitivity of 5-HT_2A receptors.  Psychopharmacol.. 2001;  159 132-136
• 4 Biggio G, Fadda F, Fanny P, Tagliamonte A, Gessa G L. Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by tryptophan-free diet.  Life Sciences. 1974;  14 1321-1329
• 5 Burns T G, Brown G M. The effeects of acute and chronic desmethylimmipramine treatment on pineal and serum melatonin and N-acetylserotonin. In: Brown GM, Wainwright SD (eds) The pineal gland: endocrine aspects. Pergamon Press Oxford; 1985: 25-30
• 6 Chi J D, Odontiadis J, Franklin M. Simultaneous determination of catecholamines in rat brain tissue by high-performance liquid chromatography.  J Chrom B. 1999;  731 361-367
• 7 Cowen P J, Fraser S, Grahame-Smith D G, Green A R, Stanford C. The effect of chronic antidepressant administration on β-adrenoceptor function in the rat pineal.  Br J Pharmac. 1983;  78 89-96
• 8 Curzon G, Freidal J, Knott P J. The effects of fatty acids on the binding of tryptophan to plasma protein.  Nature. 1973;  242 198-200
• 9 Evans G W. The effect chromium picolinate on insulin controlled parameters in humans.  Intl J Biosoc Med Res. 1989;  1 163-180
• 10 Fernstrom J D. The effect of nutritional factors on brain amino acid levels and monoamine synthesis.  Fed Proc. 1976;  35 1151-1156
• 11 Franklin M. Sub-chronic treatment effects of an extract of hypericum perforatum (ST John’s wort, LI 160) on neuroendocrine responses to the 5-HT2 agonist, DOI in the rat. Pharmacopsychiat (in press)
• 12 Franklin M. Researching the antidepressant actions of Hypericum perforatum (St John’s wort) in animals and man.  Pharmacopsychiat. 2001;  34(Suppl 1) S29-37
• 13 Gartside S E, Ellis P M, Sharp T, Cowen P J. Selective 5-HT_1A and 5-HT₂ receptor-mediated adrenocorticotropin release in the rat: effect of repeated antidepressant treatments.  Eur J Pharmacol. 1992;  221 27-33
• 14 Franklin M, Clement E M, Campling G, Cowen P J. Effect of venlafaxine on pinea; melatonin and noradrenaline in the male rat.  J Psychopharmacol. 1998;  12(4) 371
• 15 Goodman H M. The Physiologist 1970 13: 75
• 16 Jacobson A M. Depression and diabetes.  Diabetes Care. 1993;  16 1621-1623
• 17 Jovanic-Peterson L, Gutierrez M, Peterson C M. Chromium supplementation for gestational diabetic women improves glucose tolerance and decreases hyperinsulinemia (Abstract).  J Am Coll Nutr. 1995;  14 530
• 18 Kaats G R, Wise J A, Blum K. The short-term therapeutic efficacy of treating obesity with a plan of improved nutrition and moderate calorie control restriction.  Current Ther Res. 1992;  51 261-274
• 19 Klein D C, Berg G R, Weller J. Melatonin synthesis adenosine 3′,5′- monophosphate and norepinephrine stimulate N-acetyl-transferase.  Science. 1970;  168 979-980
• 20 McCarty M F. Enhancing central and peripheral insulin activity as a strategy for the treatment of endogenous depression - an adjuvant role for chromium picolinate?.  Med Hypotheses. 1994;  43 247-252
• 21 Maj J, Bijak M, Dziedzicka-Waslewska M, Rogoz R, Rogoz Z, Skuza G, Tokarski T. The effects of paroxetine given repeatedly on the 5-HT receptor subpopulations in the rat brain.  Psychopharmacol. 1996;  127 237-240
• 22 Meltzer H Y. Serotonergic function in the affective disorders: the effect of antidepressants and lithium on the 5-hydroxytryptophan-induced increase in serum cortisol.  Ann NY Acad Sci. 1984;  430 115-137
• 23 McLeod M N, Gaynes B N, Golden R N. Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients.  J Clin Psych. 1999;  60(4) 237-240
• 24 Moyer J A, Greenberg L H, Frazer A, Brunswick D J, Mendels J, Weiss B. Opposite effects of acute and repeated administration of desmethylimmipramine on adrenergic responsivness in rat pineal gland.  Life Science. 1979;  24 2237-2244
• 25 Nathan R S, Sachar E J, Asnis G M. Relative insulin insensitivity and cortisol secretion in depressed patients.  Psych Res. 1981;  4 291-300
• 26 Perez-Cruet J, Chase TN and Murphy D L. Dietary regulation of brain tryptophan metabolism by plasma ratio of free tryptophan and neutral amino acids in humans.  Nature. 1974;  248 693-695
• 27 Schwartz M W, Figlwicz D P, Baskin D G. A hormonal regulator of energy balance.  Endocr Rev. 1992;  13 387-413
• 28 Tagliamonte A, Tagliamonte P, Perez-Cruet J, Stern S, Gessa G L. Effect of psychotropic drugs on tryptophan concentration in the rat brain.  J Pharmacol Exp Ther. 1971;  177 475-480
• 29 Van de Kar L. Neuroendocrine pharmacology of serotonergic (5-HT) neurons.  Annu Rev Pharmacol Toxicol. 1991;  31 289-320
• 30 Wilkinson G, Borsey D Q, Leslie P. Psychiatric disorder in patients with insulin-dependent diabetes mellitus attending a general hospital clinic i) two-stage screening and ii) detection by physicians.  Psych Med. 1987;  17 515-517
• 31 Wright J H, Jacisin J J, Radin N S. Glucose metabolism in unipolar depression.  Brit J Psych. 1978;  132 386-393