EFFECT OF PRENATAL TREATMENT WITH METHYLAZOXYMETHANOL ON CARBACHOL-STIMULATED, NOREPINEPHRINE-STIMULATED AND GLUTAMATE-STIMULATED PHOSPHOINOSITIDE METABOLISM IN THE NEONATAL, YOUNG, AND ADULT OFFSPRING

Carbachol-, norepinephrine-land glutamate-stimulated phosphoinositide metabolism was investigated in the neonatal, young and adult cerebral cortex slices of rats prenatally treated with methylazoxymethanol (MAM ) on gestational day 15 (GD15) or GD19. In rat offspring treated on GD 15 there was a significant reduction in the accumulation of [H-3]inosi tol phosphates induced by carbachol and a significant increase in the accumulation of [H-3]inositol phosphates induced by norepinephrine on day 7, whereas no changes were observed at the other ages. No signific ant changes, on the other hand, were observed for glutamate-stimulated phosphoinositide metabolism in GD15 treated rats and for carbachol-, norepinephrine- and glutamate-stimulated phosphoinositide metabolism i n animals treated on GD19 at any of the different ages evaluated. Thes e results indicate that treatment with MAM on GD15, which results in a marked microencephaly, causes a marked alteration of muscarinic and a lpha(1)-adrenergic receptor-stimulated phosphoinositide metabolism dur ing brain development and that these alterations undergo adaptive chan ges in the adult brain.