CHRONIC NEONATAL NMDA RECEPTOR BLOCKADE WITH MK-801 ALTERS MONOAMINE METABOLISM IN THE ADULT-RAT

Administration of non-competitive N-methyl-D-aspartate (NMDA) antagoni sts in rodents leads to a characteristic motor syndrome which has been related to changes in monoamine metabolism in a variety of brain regi ons. We examined the question whether chronic MK-801 treatment in neon atal rats from postnatal day 8 through 19, which has been shown previo usly to alter NMDA receptor function, would also affect monoamine meta bolism in striatum and frontal cortex of adult rats. Monoamines and th eir metabolites were determined 5 months after the treatment using hig h-performance liquid chromatography with electrochemical detection. Di hydroxyphenylacetic acid (DOPAC) concentration was elevated (> 40%) in both regions tested, while 5-hydroxyindoleacetic acid (5-HIAA) concen tration was significantly elevated only in the cortex (19%), and 3-met hoxy-4-hydroxyphenylglycol (MHPG) only in the striatum (47%). These re sults demonstrate that the long-lasting effects of chronic neonatal MK -801 treatment are not restricted to glutamate transmission, but inclu de monoamine transmission as well.