CHRONIC NEONATAL BLOCKADE OF N-METHYL-D-ASPARTATE RECEPTOR BY CGP-39551 INCREASES DOPAMINERGIC FUNCTION IN ADULT-RAT

Following chronic neonatal treatment with the competitive N-methyl-D-a spartate antagonist CGP 39551, adult rats showed increased behavioral responses to the D-2 dopamine receptor stimulation. In nucleus accumbe ns and in n. striatum of similarly treated rats increases in D-2 dopam ine receptor number were observed. CGP 39551 was administered daily to neonatal rats with increasing doses from postnatal day 1 to 22. At po stnatal days 70-82, the rats were observed for hyperactivity induced b y the selective D-2 dopamine receptor agonist LY 171555, the grooming behavior elicited by the specific D-1 dopamine receptor stimulating ag ent SKF 38393 and the stereotypies induced by the mixed D-1/D-2 recept or agonist apomorphine. [H-3]Spiroperidol and [H-3]SCH 23390 specific binding to membranes of nucleus accumbens, nucleus striatum and fronta l cortex of similarly treated rats was measured. The hypermotility and the stereotyped behavior induced by LY 171555 and apomorphine, respec tively, were augmented, whereas grooming behavior elicited by SKF 3839 3 was unaffected, in CGP 39551-treated rats. Consistently, both in nuc leus accumbens and in n. striatum an increase in [H-3]Spiroperidol spe cific binding was observed, while [H-3]SCH 23390 specific binding did not change. The study demonstrates that chronic blockade of N-methyl-D -aspartate receptor during the critical period of brain maturation res ults in long-lasting dopaminergic functional changes.