DEVELOPMENTAL-CHANGES IN [H-3] LYSERGIC-ACID DIETHYLAMIDE ([H-3]LSD) BINDING TO SEROTONIN RECEPTORS IN THE HUMAN BRAIN-STEM

The ontogeny of serotonin receptors in the human brainstem is largely unknown, despite the putative roles of serotonin in neural development , synaptic transmission, brainstem modulation of vegetative functions, and clinical disorders of serotonergic function. This study provides baseline information about the quantitative distribution of [H-3]LSD b inding to serotonergic receptors (5-HT1A-1D 5-HT2) in the human brains tem, from midgestation through maturity, with a focus upon early infan cy. Brainstems were analyzed from 5 fetuses (19-25.5 weeks postconcept ion), 5 infants (42-55.5 weeks postconception), and 3 mature individua ls (4, 20, and 52 years). Tissue autoradiography was used with [H-3]LS D for total serotonergic receptor binding and [H-1]LSD and serotonin f or nonspecific binding; computer-based quantitation was applied. The h ighest levels of [H-3]LSD binding occurred prenatally throughout the b rainstem. At all ages, the highest relative binding localized to the r ostral raphe. A marked decline in [H-3]LSD binding occurred between th e midgestation and infancy in brainstem regions involved in control of cardiovascular function, respiration, and pain. The fetal peak in [H- 3]LSD binding to 5-HT receptors is consistent with a trophic role of s erotonin in immature human brainstem, and a decrease, between midgesta tion and infancy, in serotonergic modulation of vegetative functions c ontrolled by the brainstem.