DEVELOPMENTAL-CHANGES IN NEUROTRANSMITTER RECEPTOR-BINDING IN THE HUMAN PERIAQUEDUCTAL GRAY

The periaqueductal gray (FAG) plays a central role in the integration of defense responses to threatening or stressful stimuli. Little is kn own about the neurochemical development of the human FAG around the ti me of birth, when the fetus makes the transition to extrauterine life and independent defense responses are needed. We analyzed receptor bin ding to selected neurotransmitters implicated in FAG function in 7 fet uses (19 to 26 gestational weeks), 9 infants (38 to 74 postconceptiona l weeks), 1 child (4 years), and 3 adults (20 to 68 years). Tissue aut oradiography was used with radioligands for opioid, nicotinic, muscari nic, kainate, and serotoninergic receptors. By midgestation, binding t o nicotinic, muscarinic, serotoninergic, opioid, and kainate receptors is already localized to the human FAG. The subsequent developmental p rofiles are unique for each radioligand. Binding to nicotinic and sero toninergic receptors decreases significantly from the fetal to mature periods, but at different tempos. In contrast, there is no significant change from midgestation to infancy for muscarinic, kainate, and opio id binding: between infancy and the mature period there is a downward trend in binding for muscarinic and kainate receptors and an upward tr end for opioid receptors. This study provides baseline information abo ut the neurochemical development of the human FAG in early life. This information is of value in considering the neurochemical substrate of the maturation of defense responses in human infancy, and in evaluatin g potential neurochemical disorders of the developing human PAG.