Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats.
Effects of single subcutaneous doses of sodium 2,4-dichlorophenoxyacetate (2,4-D-Na) on biogenic amines and their acidic metabolites in rat brain and cerebrospinal fluid (CSF) were analyzed by high pressure liquid chromatography. After 200 mg/kg 2,4-D-Na, the cerebral concentration of 5-hydroxytryptamine (5-HT) was increased slightly and that of 5-hydroxyindoleacetic acid (5-HIAA) roughly 3-fold between 1 and 8 h after the administration. There was also a tendency towards slightly lowered dopamine (DA) levels. No statistically significant changes in brain concentrations of noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or tryptophan (TRY) were found. At the same time, however, the maximal increase in DOPAC, HVA and 5-HIAA concentrations in the CSF was 2.3-5.8-fold. The dependency of biogenic amines and metabolites on 2,4-D-Na dose was studied by injecting s.c. 0, 10, 30 and 100 mg/kg and sacrificing the rats at 2 h. In the brain, there was a dose-dependent increase in concentrations of 5-HIAA (at the two highest doses) and HVA (at the highest dose) while in the CSF those of all three acidic metabolites increased at the two highest doses. The 10 mg/kg dose had no effect. The results agree with the hypothesis that 2,4-D inhibits the organic acid transport out of the brain, which should then result in increased cerebral levels of acidic metabolites of biogenic amines, but it may also have effects on the activity of serotoninergic and dopaminergic neurones.
Elo
H A
HA
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
MacDonald
E
E
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D004563:Electrochemistry; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014363:Tryptamines / Q000378:metabolism
D001679:Biogenic Amines; D014363:Tryptamines; D015102:3,4-Dihydroxyphenylacetic Acid; D015084:2,4-Dichlorophenoxyacetic Acid; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid