Pm. Whitakerazmitia et al., EFFECTS OF GESTATIONAL EXPOSURE TO MONOAMINE-OXIDASE INHIBITORS IN RATS - PRELIMINARY BEHAVIORAL AND NEUROCHEMICAL STUDIES, Neuropsychopharmacology, 11(2), 1994, pp. 125-132
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.