Monoamine oxidase inhibition during brain development induces pathological aggressive behavior in mice.
BACKGROUND
Monoamine oxidase (MAO) is historically a focus of concern in research on impulsive and aggressive behavior. Recent studies in a single kindred with a point mutation in the MAO-A gene, together with phenotypic evaluations of MAO-A knockout mice, have sharpened this interest. The goal of this study was to investigate the behavioral consequences of MAO inhibition during brain development and to determine the extent to which specific effects could be attributed to MAO- A versus MAO-B.


METHODS
MAO-A and B inhibitors were administered, separately or in combination, during gestation and lactation. Behavioral evaluations included neurologic testing, delay of rewarded response, and the resident-intruder aggression paradigm, conducted before and after an acute pharmacologic challenge.


RESULTS
Total prenatal MAO inhibition produced a pervasive increase in aggressive behavior, whereas MAO-B inhibited mice demonstrated a similar pattern of lower intensity. Aggression was elevated in MAO-A inhibited mice only after acute pharmacologic challenge, suggesting prenatal sensitization.


CONCLUSIONS
Developmental inhibition of MAO activity engenders behavioral effects that parallel those observed in animals with genetic ablation of MAO function. These data underscore the importance of neurochemical changes during development and provide a possible model for disinhibited aggression, common in clinical populations.
Mejia
Jose Maria
JM
Department of Biology, McGill University, 1033 Pine Avenue West, Montréal, Québec H3A 1A1, Canada.
Ervin
Frank R
FR
Baker
Glen B
GB
Palmour
Roberta M
RM
D000374:Aggression; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D005260:Female; D007774:Lactation / Q000378:metabolism; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase