ONTOGENY OF 5-HYDROXYTRYPTAMINE(2) RECEPTOR IMMUNOREACTIVITY IN THE DEVELOPING RAT-BRAIN

In this study, we investigated the regional and temporal emergence of 5-hydroxytryptamine, receptor immunoreactivity in the developing rat b rain. In a qualitative immunocytochemical analysis using an antibody a gainst the rat 5-hydroxytryptamine2 receptor protein, we visualized ce lls 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-hyd roxytryptamine2 receptors were identified: the time of onset, a period of accelerated expression and hyper-elaboration, and a period of regr ession. In general, the onset of 5-hydroxytryptamine2 receptor immunor eactivity occurred relatively late in the ontogeny of cells in these r egions, in the late prenatal and early postnatal periods. Following th e perinatal onset of receptor expression, there was a rapid increase i n the number of immunoreactive neurons during the first week after bir th. In neocortex, there appeared to be a relative over-expression of t he receptor, with an elevated density and hyper-elaboration of immunop ositive neurons relative to the adult, reaching a peak at the end of t he 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-hydr oxytryptamine2 receptor were first detected within the regions in whic h they would ultimately reside, and after the known periods of cell pr oliferation for these regions. These observations would argue against a role for the 5-hydroxytryptamine2 receptor as a transducer of the ea rly developmental influences of serotonin in the central nervous syste m, 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 receptor s suggests time-points at which events that disrupt the normal ontogen etic pattern of expression could produce long-lasting effects on centr al serotonergic neurotransmission.