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Eur J Pharmacol. 2014 Dec 15;745:76-83. doi: 10.1016/j.ejphar.2014.10.014. Epub 2014 Oct 17.

Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

Author information

1
Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga LV-1586, Latvia.
2
Department of Pathology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga, LV-1586, Latvia; Riga East University Hospital, Center of Pathology, 2 Hipokrata str., LV-1038 Riga, Latvia.
3
Department of Pharmacology, Faculty of Medicine, University of Latvia, 19, Raina blv., Riga LV-1586, Latvia. Electronic address: vijaklus@latnet.lv.

Abstract

The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol.

KEYWORDS:

Haloperidol; Haloperidol (PubChem CID: 3559); Memory; Mildronate; Mildronate (PubChem CID: 123868); Protein expression; Stress

PMID:
25446926
DOI:
10.1016/j.ejphar.2014.10.014
[Indexed for MEDLINE]

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