Early developmental modulation of GABAA receptor function. Influence on adaptive responses.

Abstract

If GABA is serving a trophic role during early brain development, before taking on its function as a neurotransmitter, interference with the function of GABA during this period should have a profound influence on neural organization. We have addressed this hypothesis by evaluating the effects of exposing rat fetuses to diazepam (DZ), a positive modulator of GABA at the GABAA receptor, over gestation days 14 to 20. Studies have shown that adult rats exposed in utero to DZ over this developmental period make inappropriate behavioral responses and have altered neural and hormonal responses to environmental stimuli that threaten the organism's stability and homeostasis. Thus, the early exposure led to altered adaptive responses. These effects of the early exposure did not become apparent until late in adolescent development. Furthermore, specific behavioral and neural responses to environmental challenges normally emerge over adolescent development. Other studies have shown that the GABAA receptor in adult brains is responsive to environmental challenges. Thus, we hypothesize that early modulation of the action of GABA mediated via the GABAA receptor interfered with the neural organization of adaptive responses.