EFFECTS OF GESTATIONAL EXPOSURE TO MONOAMINE-OXIDASE INHIBITORS IN RATS - PRELIMINARY BEHAVIORAL AND NEUROCHEMICAL STUDIES

Monoamine neurotransmitters are important in the development of the im mature mammalian brain, prior to assuming their role as neurotransmitt ers. The endogenous levels of these transmitters are highly regulated by the enzyme monoamine oxidase (MAO). Thus, any change in this enzyme should have a profound effect on brain development. In order to test this hypothesis, we treated developing rat pups with the monoamine oxi dase inhibitors (MAO-is), clorgyline (MAO-A, 3 mg/kg), and deprenyl (M AO-B, 3 mg/kg) throughout gestation (MAO-I-birth), or throughout gesta tion and to sacrifice (MAO-I-sac). The animals were analyzed for serot onin and dopamine terminal density, using H-3-paroxetine and H-3-GBR 1 2935, respectively. Whereas there were no changes in the development o f the dopamine system, the serotonin system was severely affected, par ticularly in the cortex that showed a significant reduction of innerva tion at 30 days postnatal. The animals reached all normal development milestones on schedule, and had no changes in measures of anxiety (% l ight/dark); however, the animals showed increased open field activity and deficits in a passive avoidance paradigm, which may be a measure o f impulsivity. The MAO-I-sac animals were severely impaired, showing s tereotypic behavior, seizures, and eventually visual impairments. Our results are discussed in terms of relevance to human disease states, s uch as atypical Norrie's disease, impulsivity, and hyperactivity. As w ell, our results should be used to caution against the use of MAO-is i n women of child-bearing age.