Summary
The effect of 3,3′,5-triiodo-l-thyronine (T3) on working memory in ethylcholine aziridinium ion (AF64A)-treated mice was studied in a delayed nonmatching to sample task using a T-maze. After behavioural testing was completed, mice were killed by microwave irradiation and regional brain levels of acetylcholine, aspartate, glutamate, glutamine, glycine, taurine, and γ-aminobutyric acid (GABA) were measured by high-performance liquid chromatography with electrochemical detection. Treatment with AF64A (7 nmol, i. c. v.) produced a deficit in working memory performance in the non-matching to sample task at 30 s delay, and decreased acetylcholine, glutamate, and GABA levels in the hippocampus, but not in the septum and cerebral cortex. Administration of T3 (0.3 mg/kg, p.o., once daily for 6 days) to AF64A-treated animals improved the deficit in working memory performance and reversed the decrease in acetylcholine, glutamate, and GABA levels in the hippocampus. These results indicate that the deficit in performance induced by AF64A can be improved by T3 administration.
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References
Chrobak JJ, Hanin I, Walsh TJ (1987) AF64A (ethylcholine aziridinium ion), a cholinergic neurotoxin, selectively impairs working memory in a multiple component T-maze task. Brain Res 414:15–21
Fisher A, Mantione RC, Abraham JD, Hanin I (1982) Long term central cholinergic hypofunction induced in mice by ethylcholine aziridium ion (AF64A) in vivo. J Pharmacol Exp Ther 222:140–145
Hörtnagl H, Berger ML, Reither H, Hornykiewicz O (1991) Cholinergic deficit induced by ethylcholine aziridinium (AF64A) in rat hippocampus: effect on glutaminergic systems. Naunyn-Schmiedeberg's Arch Pharmacol 344:213–219
Kalaria RN, Prince AK (1985) The effects of neonatal thyroid deficiency on acetylcholine synthesis and glucose oxidation in rat corpus striatum. Dev Brain Res 20:271–279
Leventer SM, Wulfert E, Hanin I (1987) Time course of ethylcholine aziridium ion (AF64A)-induced cholinotoxicity in vivo. Neuropharmacology 26:361–365
Masuda Y, Murai S, Saito H, Abe E, Kohori I, Itoh T (1992) A simple method used a housing in a maze for estimating working memory of mice. Jpn J Psychopharmacol 12:27–32
McGurk SR, Hartgraves SL, Kelly PH, Gordon MN, Butcher LL (1987) Is ethylcholine mustard aziridium ion a specific cholinergic neurotoxin? Neuroscience 22:215–224
Murai S, Miyate H, Saito H, Nagahama H, Masuda Y, Itch T (1989) Simple determination of acetylcholine and choline within 4 minutes by HPLC-ECD and immobilized enzyme column in mice brain areas. J Pharmacol Methods 21:255–262
Murai S, Saito H, Abe E, Masuda Y, Itch T (1992) A rapid assay for neurotransmitter amino acids, aspartate, glutamate, glycine, taurine and γ-aminobutyric acid in the brain by high-performance liquid chromatography with electrochemical detection. J Neural Transm 87:145–153
Olton DS, Schlosberg P (1978) Food-searching strategies in young rats: win-shift predominates over win-stay. J Comp Physiol Psychol 92:609–618
Patel AJ, Hayashi M, Hunt A (1988) Role of thyroid hormone and nerve growth factor in the development of choline acetyltransferase and other cell specific marker enzymes in the basal forebrain of the rat. J Neurochem 50:803–811
Rami A, Rabie A, Patel AJ (1986) Thyroid hormone and development of the rat hippocampus: cell acquisition in the dentate gyrus. Neuroscience 19:1207–1216
Slotnick BM, Leonard CM (1975) A stereotaxic atlas of the albino mouse forebrain. US Deparment of Health, Education, and Welfare. Public Health Service. Alcohol, Drug Abuse, and Mental Health Administration. Rockville, Md
Squire LR, Zola-Morgan S (1985) The neuropsychology of memory: new links between humans and experimental animals. In: Olton DS, Gamzu E, Corkin S (eds) Memory dysfunctions: an integration of animal and human research from preclinical and clinical perspectives. The New York Academy of Sciences, New York, pp 137–149
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Correspondence to: E. Abe at the above address
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Abe, E., Murai, S., Masuda, Y. et al. Reversal by 3,3′,5-triido-l-thyronine of the working memory deficit, and the decrease in acetylcholine, glutamate and γ-aminobutyric acid induced by ethylcholine aziridinium ion in mice. Naunyn-Schmiedeberg's Arch Pharmacol 346, 238–242 (1992). https://doi.org/10.1007/BF00165308
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DOI: https://doi.org/10.1007/BF00165308