Monoamine neurotransmitter metabolism in microencephalic rat brain after prenatal methylazoxymethanol treatment.

Administration of methylazoxymethanol (MAM) in the fetal stage leads to forebrain microencephaly with a severe atrophy in cerebral cortex, striatum, and hippocampus. The concentration of endogenous monoamines was markedly increased in the atrophic regions while total amount was largely unchanged. Striatal dopamine and cortical noradrenaline nerve terminals from MAM treated animals showed unaltered sedimentation properties in a sucrose density gradient and were estimated to have normal transmitter levels. gamma-Butyrolactone induced increase in dopamine levels and its counteraction by apomorphine was essentially unaltered after MAM. These data give further support for the view that the monoamine nerve terminal fields develop to their normal size in the atrophic regions leading to a hyperinnervation. Analysis of monoamine metabolite levels, increase of monoamines after monoamine oxidase inhibition, and disappearance of catecholamines after tyrosine hydroxylase inhibition were conducted to obtain information on monoamine turnover. The results indicated an essentially unaltered, or a small reduction of, monoamine turnover in the atrophic regions when calculated per monoamine nerve terminal, while increased when calculated per unit weight of the tissue.