Effect of neonatal nomifensine exposure on adult behavior and brain monoamines in rats

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Abstract
The aim of the study was to examine the effects of early postnatal exposure to nomifensine, an inhibitor of catecholamine uptake, on concurrent active (REM) sleep, on later alcohol related behavior and on monoamine concentrations in various brain regions of rats. For these purposes rats were given daily injections of 10 mg/kg nomifensine s.c. between the 7th and the 18th postnatal days. During the nomifensine exposure active sleep, expressed as a percentage of total sleeping time, was reduced. At one month of age, the nomifensine rats showed increased ambulation and had lower defecation scores in the open-field than the controls. Neonatal exposure to nomifensine increased voluntary intake of 10% (v/v) alcohol when the rats were 2–3 months of age. The rats, however, did not exhibit perseveration in the T-maze, and similarly to control rats suppressed drinking 0.1 M lithium chloride even when thirsty. Measurement of cerebral monoamine concentrations at the age of 3 months suggested that neonatal nomifensine treatment interferes with the noradrenergic and serotonergic systems in several regions of the brain. Concentrations of noradrenaline and 5-hydroxy-indoleacetic acid (5-HIAA) were decreased in the cerebral cortex and frontal cortex, concentration of 5-HIAA was decreased in the neostriatum, and concentrations of noradrenaline, 5-hydroxytryptamine (5-HT) and 5-HIAA were elevated in the lower brain stem. Taken together, these findings show that exposure to nomifensine during the 2nd and 3rd postnatal weeks suppresses neonatal active sleep, causes changes in the adult open-field behavior, and increases voluntary alcohol intake, perhaps due to a long-lasting alteration in brain monoamines.