Ontogeny of 5-hydroxytryptamine₂ receptor immunoreactivity in the developing rat brain

In this study, we investigated the regional and temporal emergence of 5-hydroxytryptamine₂ receptor immunoreactivity in the developing rat brain. In a qualitative immunocytochemical analysis using an antibody against the rat 5-hydroxytryptamine₂ receptor protein, we visualized cells expressing the receptor in the pontine tegmentum, caudate nucleus, basal forebrain, hippocampus and neocortex of developing rats. Three potentially important periods in the developmental regulation of 5-hydroxytryptamine₂ receptors were identified: the time of onset, a period of accelerated expression and hyperelaboration, and a period of regression. In general, the onset of 5-hydroxytryptamine₂ receptor immunoreactivity occurred relatively late in the ontogeny of cells in these regions, in the late prenatal and early postnatal periods. Following the perinatal onset of receptor expression, there was a rapid increase in the number of immunoreactive neurons during the first week after birth. In neocortex, there appeared to be a relative over-expression of the receptor, with an elevated density and hyper-elaboration of immunopositive neurons relative to the adult, reaching a peak at the end of the second week. There was then a gradual decrease in both the density and morphological complexity of cortical 5-hydroxytryptamine₂-labelled neurons, until the adult pattern of expression was achieved at about four weeks of age. In all areas studied, cells positive for the 5-hydroxytryptamine₂ receptor were first detected within the regions in which they would ultimately reside, and after the known periods of cell proliferation for these regions. These observations would argue against a role for the 5-hydroxytryptamine₂ receptor as a transducer of the early developmental influences of serotonin in the central nervous system, but leave open the possibility that the receptor may participate in regulating some aspect of terminal differentiation or late maturation of the neurons on which it is found. The identification of important developmental periods in the ontogeny of 5-hydroxytryptamine₂ receptors suggests time-points at which events that disrupt the normal ontogenetic pattern of expression could produce long-lasting effects on central serotonergic neurotransmission.