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A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania.
Int J Neuropsychopharmacol. 2018 05 01; 21(5):473-484.IJ

Abstract

Background

Casein glycomacropeptide is a peptide that lacks phenylalanine, tyrosine, and tryptophan. This profile may enable it to deplete phenylalanine, tyrosine, and tryptophan, and subsequently the synthesis of dopamine and serotonin in the brain. Dopamine- and serotonin-depleting amino acid mixtures have shown promise as acute antimanic treatments. In this study, we explore the depleting effects on amino acids, dopamine and serotonin as well as its actions on manic-like and other behavior in rats.

Methods

Casein glycomacropeptide and a selection of amino acid mixtures were administered orally at 2, 4, or 8 h or for 1 week chronically. Amino acid and monoamine levels were measured in plasma and brain and behavior was assessed in the amphetamine-hyperlocomotion, forced swim, prepulse inhibition, and elevated plus maze tests.

Results

Casein glycomacropeptide induced a time-dependent reduction in tyrosine, tryptophan, and phenylalanine in brain and plasma which was augmented by supplementing with leucine. Casein glycomacropeptide +leucine reduced dopamine in the frontal cortex and serotonin in the hippocampus, frontal cortex, and striatum after 2 and 4 h. Casein glycomacropeptide+leucine also had antimanic activity in the amphetamine-induced hyperlocomotion test at 2 h after a single acute treatment and after 1 week of chronic treatment.

Conclusions

Casein glycomacropeptide-based treatments and a branched-chain amino acid mixture affected total tissue levels of dopamine in the frontal cortex and striatum and serotonin in the frontal cortex, striatum, and hippocampus of rats in a time-dependent fashion and displayed antimanic efficacy in a behavioral assay of mania.

Authors+Show Affiliations

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.Arla Foods Ingredients Group P/S, Denmark.Department Psychiatry Odense, Psychiatry in the Region of Southern Denmark, Denmark. Department of Psychiatry, Institute for Clinical Research, University of Southern Denmark, Denmark.Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Department of Clinical Medicine, AUGUST Centre, Aarhus University, Risskov, Denmark.Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark. Department of Clinical Medicine, AUGUST Centre, Aarhus University, Risskov, Denmark. Centre for Pharmaceutical Excellence, School of Pharmacy, North-West University, South Africa.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29726996

Citation

Liebenberg, Nico, et al. "A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania." The International Journal of Neuropsychopharmacology, vol. 21, no. 5, 2018, pp. 473-484.
Liebenberg N, Jensen E, Larsen ER, et al. A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania. Int J Neuropsychopharmacol. 2018;21(5):473-484.
Liebenberg, N., Jensen, E., Larsen, E. R., Kousholt, B. S., Pereira, V. S., Fischer, C. W., & Wegener, G. (2018). A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania. The International Journal of Neuropsychopharmacology, 21(5), 473-484. https://doi.org/10.1093/ijnp/pyy012
Liebenberg N, et al. A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania. Int J Neuropsychopharmacol. 2018 05 1;21(5):473-484. PubMed PMID: 29726996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania. AU - Liebenberg,Nico, AU - Jensen,Erik, AU - Larsen,Erik Roj, AU - Kousholt,Birgitte Saima, AU - Pereira,Vitor Silva, AU - Fischer,Christina Weide, AU - Wegener,Gregers, PY - 2017/06/10/received PY - 2018/02/06/accepted PY - 2018/5/5/entrez PY - 2018/5/5/pubmed PY - 2019/5/2/medline SP - 473 EP - 484 JF - The international journal of neuropsychopharmacology JO - Int. J. Neuropsychopharmacol. VL - 21 IS - 5 N2 - Background: Casein glycomacropeptide is a peptide that lacks phenylalanine, tyrosine, and tryptophan. This profile may enable it to deplete phenylalanine, tyrosine, and tryptophan, and subsequently the synthesis of dopamine and serotonin in the brain. Dopamine- and serotonin-depleting amino acid mixtures have shown promise as acute antimanic treatments. In this study, we explore the depleting effects on amino acids, dopamine and serotonin as well as its actions on manic-like and other behavior in rats. Methods: Casein glycomacropeptide and a selection of amino acid mixtures were administered orally at 2, 4, or 8 h or for 1 week chronically. Amino acid and monoamine levels were measured in plasma and brain and behavior was assessed in the amphetamine-hyperlocomotion, forced swim, prepulse inhibition, and elevated plus maze tests. Results: Casein glycomacropeptide induced a time-dependent reduction in tyrosine, tryptophan, and phenylalanine in brain and plasma which was augmented by supplementing with leucine. Casein glycomacropeptide +leucine reduced dopamine in the frontal cortex and serotonin in the hippocampus, frontal cortex, and striatum after 2 and 4 h. Casein glycomacropeptide+leucine also had antimanic activity in the amphetamine-induced hyperlocomotion test at 2 h after a single acute treatment and after 1 week of chronic treatment. Conclusions: Casein glycomacropeptide-based treatments and a branched-chain amino acid mixture affected total tissue levels of dopamine in the frontal cortex and striatum and serotonin in the frontal cortex, striatum, and hippocampus of rats in a time-dependent fashion and displayed antimanic efficacy in a behavioral assay of mania. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/29726996/A_Preclinical_Study_of_Casein_Glycomacropeptide_as_a_Dietary_Intervention_for_Acute_Mania L2 - https://academic.oup.com/ijnp/article-lookup/doi/10.1093/ijnp/pyy012 DB - PRIME DP - Unbound Medicine ER -