Chronic neonatal NMDA receptor blockade with MK-801 alters monoamine metabolism in the adult rat.
Administration of non-competitive N-methyl-D-aspartate (NMDA) antagonists in rodents leads to a characteristic motor syndrome which has been related to changes in monoamine metabolism in a variety of brain regions. We examined the question whether chronic MK-801 treatment in neonatal rats from postnatal day 8 through 19, which has been shown previously to alter NMDA receptor function, would also affect monoamine metabolism in striatum and frontal cortex of adult rats. Monoamines and their metabolites were determined 5 months after the treatment using high-performance liquid chromatography with electrochemical detection. Dihydroxyphenylacetic acid (DOPAC) concentration was elevated (greater than 40%) in both regions tested, while 5-hydroxyindoleacetic acid (5-HIAA) concentration was significantly elevated only in the cortex (19%), and 3-methoxy-4-hydroxyphenylglycol (MHPG) only in the striatum (47%). These results demonstrate that the long-lasting effects of chronic neonatal MK-801 treatment are not restricted to glutamate transmission, but include monoamine transmission as well.
Gorter
J A
JA
Netherlands Institute for Brain Research, Amsterdam.
Botterblom
M H
MH
Feenstra
M G
MG
Boer
G J
GJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001259:Ataxia / Q000139:chemically induced / Q000378:metabolism; D001679:Biogenic Amines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D006130:Growth Disorders / Q000139:chemically induced; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D009748:Nutrition Disorders / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D001679:Biogenic Amines; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D016291:Dizocilpine Maleate; D004298:Dopamine; D009638:Norepinephrine