Effects of gestational exposure to monoamine oxidase inhibitors in rats: preliminary behavioral and neurochemical studies.
Monoamine neurotransmitters are important in the development of the immature mammalian brain, prior to assuming their role as neurotransmitters. 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 oxidase inhibitors (MAO-Is), clorgyline (MAO-A, 3 mg/kg), and deprenyl (MAO-B, 3 mg/kg) throughout gestation (MAO-I-birth), or throughout gestation and to sacrifice (MAO-I-sac). The animals were analyzed for serotonin and dopamine terminal density, using 3H-paroxetine and 3H-GBR 12935, respectively. Whereas there were no changes in the development of the dopamine system, the serotonin system was severely affected, particularly in the cortex that showed a significant reduction of innervation at 30 days postnatal. The animals reached all normal development milestones on schedule, and had no changes in measures of anxiety (% light/dark); however, the animals showed increased open field activity and deficits in a passive avoidance paradigm, which may be a measure of impulsivity. The MAO-I-sac animals were severely impaired, showing stereotypic behavior, seizures, and eventually visual impairments. Our results are discussed in terms of relevance to human disease states, such as atypical Norrie's disease, impulsivity, and hyperactivity. As well, our results should be used to caution against the use of MAO-Is in women of child-bearing age.
Department of Psychiatry and Behavioral Sciences, SUNY, Stony Brook 11794-8101.
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Whitaker-Azmitia
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Zhang
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Clarke
D000818:Animals; D001007:Anxiety / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D003010:Clorgyline / Q000494:pharmacology; D005260:Female; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D004856:Postural Balance / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D012727:Sex Characteristics; D012903:Smell / Q000187:drug effects
D008996:Monoamine Oxidase Inhibitors; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012642:Selegiline; D008995:Monoamine Oxidase; D003010:Clorgyline