Alterations in the metabolism of serotonin and dopamine in the central nervous system of mice displaying a persistent dyskinesia due to crotononitrile or 2-pentenenitrile.
The effect of crotononitrile (4.22 mmol/kg, CRN) or 2-pentenenitrile (2.00 mmol/kg, 2-PN), which exhibit long-term dyskinesia, was examined on the metabolism of serotonin (5-HT) and dopamine (DA) in five brain regions of mice 1, 5, 12 and 35 days after dosing with CRN or 2-PN or vehicle (0.1 ml/25 g). One day after injection, CRN increased the level of the following substances and the ratio of 5-hydroxyindoleacetic acid (5-HIAA)/5-HT: 5-HT in medulla oblongata plus pons (144% of control); 5-HIAA in cortex (162%), striatum (166%), medulla oblongata plus pons (212%), hypothalamus (146%) and mid-brain (167%); 5-HIAA/5-HT in medulla oblongata plus pons (148%) and midbrain (133%). The changes caused by 2-PN were as follows: DA levels in cortex (176% of control, 35 days after dosing); HVA levels in striatum (136%, 1 day); 5-HT levels in hypothalamus (141%, 35 days); 5-HIAA levels in striatum (150%, 1 day), medulla oblongata plus pons (159%, 1 day) and midbrain (146%, 1 day); 5-HIAA/5-HT in striatum (153%, 1 day) and midbrain (134%, 1 day). The results suggest that changes in the 5-HT system are involved in the appearance of the dyskinetic syndrome which was seen in mice 1-2 days after dosing with CRN or 2-PN.
Tanii
H
H
Department of Hygiene, School of Medicine, Kanazawa University, Japan.
Hayashi
M
M
Hashimoto
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism*
D009570:Nitriles; C062712:2-pentenenitrile; D012701:Serotonin; C031103:crotononitrile; C015660:allyl cyanide; D004298:Dopamine