Summary
A relatively high dose of amantadine (100 mg/kg i.p.) causes rigidity with humpback and tremor-like movements, but at a milder degree than harmaline. The amantadine induced syndrome is later accompanied with locomotor hyperactivity. Biochemically amantadine produces an increase of acetylcholine (ACh) content (100%) in the striatum, but with no effect on the striatal serotonin or dopamine, while GABA is increased 17% in striatum and 23% in substantia nigra. The enzyme activities involved in synthesis and degradation of ACh and GABA, namely glutamic acid decarboxylase, GABA-transaminase, and cholineacetyltransferase, are not altered after amantadine hydrochloride. The acetylcholinesterase activity in the striatum appears to show a slight decrease. The rigidity and the tremor-like movements after amantadine can be explained by the increased striatal acetylcholine as in the case of harmaline. The locomotor hyperactivity and the circling movements after amantadine hydrochloride may result from the inhibition of recurrent nigro striatal (dopaminergic) fibers influenced by the increased GABA activity in the substantia nigra, thereby causing disinhibition of the pallidar structures for locomotor activity. The cause of stereotypy and convulsions requires further investigations.
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Abbreviations
- ACh:
-
acetylcholine
- AChase:
-
acetylcholinesterase
- ChAc:
-
choline acetyltransferase
- DA:
-
dopamine
- L-Dopa:
-
3,4,-dihydroxyphenylalanine
- GABA:
-
γ-aminobutyric acid
- GABA-T:
-
L-glutamic-γ-aminobutyric transaminase
- GAD:
-
L-glutamic acid decarboxylase
- 5-HT:
-
5-hydroxytryptamine (= serotonin)
- MAO:
-
mcnoamine oxidase
- PALP:
-
pyridoxal phosphate
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Dr. Kataoka was on leave of absence from the University of Kyoto, Medical School, Department of Physiology, Japan.
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Bak, I.J., Hassler, R., Kim, J.S. et al. Amantadine actions on acetylcholine and GABA in striatum and substantia nigra of rat in relation to behavioral changes. J. Neural Transmission 33, 45–61 (1972). https://doi.org/10.1007/BF01244727
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DOI: https://doi.org/10.1007/BF01244727