Regional neurochemical studies on the effect of beta, beta'-iminodipropionitrile (IDPN) in the rat.
A permanent hyperkinetic syndrome, characterized by excitation, choreiform head and neck movements and circling, which has led to it being called collectively the "ECC-syndrome," is induced in rats by the daily IP administration of beta, beta'-iminodipropionitrile (IDPN), 300 mg/kg, for 7 days. The levels of the biogenic amines, norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), were measured in the striatum, midbrain, medulla, cortex, and cerebellum on the day the syndrome appeared (day 7) and one week later (day 14). The biogenic amine most affected by IDPN administration was 5-HT. On day 7, striatal 5-HT levels increased and 5-HIAA levels decreased while in the medulla and midbrain, 5-HIAA levels increased. On day 14, significant reductions in both 5-HT, in the midbrain, striatum, and cortex, and 5-HIAA, in all regions except the cortex, were observed. NE was markedly increased in the medulla, midbrain, and striatum on day 7, whereas on day 14 it was found to be within the normal range in these same regions. With the exception of a slight, but significant, increase in the cortex on day 7, DA levels in all regions were found to be relatively unaffected by IDPN administration on both day 7 and day 14. In an attempt to detect degenerative changes which might be taking place in the brain and which might provide an explanation for the permanency of the behavioral disturbances, the uptake of [3H]-labeled NE, DA, and 5-HT into synaptosomal-rich preparations of striatum and the uptake of NE and 5-HT into the midbrain area were compared between normal and syndromized rats on both day 7 and day 14. Small changes were observed but they were not statistically significant. The alterations of 5-HT and 5-HIAA levels in several regions of the brain under the conditions examined may indicate that IDPN's neurotoxicity primarily affects 5-HT-containing neurones. The active membrane transporting system of the nerve endings studied, however, remained relatively intact. This latter finding eliminates the possibility that neuronal degeneration in these areas is responsible for the decreased 5-HT and 5-HIAA levels or is the pathology underlying the permanency of the syndrome. These results are evaluated in terms of a possible model for hyperkinetic disorders.
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D002746:Chlorpromazine / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D009570:Nitriles; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013577:Syndrome
D001679:Biogenic Amines; D009570:Nitriles; D012701:Serotonin; D002746:Chlorpromazine; D004298:Dopamine; D009638:Norepinephrine