Influences of Intrauterine Ethanol on the Maturation of the Monoaminergic Systems in the Developing Rat Brain

Abstract

The aim of the present work was to conduct a simultaneous study of the levels of the major transmitters of the brain monoaminergic system, their metabolites, catechol-O-methyltransferase (COMT) activity, and the state of different dopamine receptor subtypes (D1 ,D 2L ,D 2S ,D 4, and D5) in the developing brains of the offspring of maternal rats alcoholized during pregnancy and lactation. Alcoholization of rats during pregnancy decreased the activities of the brain monoaminergic systems, which was manifest as decreases in the noradrenaline and dopamine (DA) levels in alcoholized fetuses, along with decreases in mRNA for the catecholamine-metabolizing enzyme COMT in forebrain structures on day 17 but not on day 13 of prenatal development. There were parallel increases in the contents of mRNA for the long and short splice variants of the type D2 dopamine receptor. During the postnatal period (days 4, 10, and 17), there was a further reduction in the activity of the DA system, and particularly reductions in the dihydroxyphenylacetic acid (DHPAA) level and the DHPAA/DA ratio in rat pups whose mothers had consumed alcohol during pregnancy but transferred to water after birth of their offspring. The activity of the serotonin system during the postnatal period of development in alcoholized rat pups was also decreased, which was apparent at the earliest stages of postnatal development (day 4 of life). Measures of serotonin metabolism then normalized. Thus, the activity of the serotonin system showed greater changes at the early periods of postnatal development (day 4), while suppression of the activity of the DA system was more marked at later stages (day 10 of life).