Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat

Light and electron microscope immunocytochemistry with a monoclonal antibod y against the N-terminal domain of the human protein was used to determine the cellular and subcellular localization of serotonin 5-HT2A receptors in the central nervous system of adult rat. Following immunoperoxidase or silv er-intensified immunogold labeling, neuronal, somatodendritic, and/or axona l immunoreactivity was detected in numerous brain regions, including all th ose in which ligand binding sites and 5-HT2A mRNA had previously been repor ted. The distribution of 5-HT2A-immunolabeled soma/dendrites was characteri zed in cerebral cortex, olfactory system, septum, hippocampal formation, ba sal ganglia, amygdala, diencephalon, cerebellum, brainstem, and spinal cord . Labeled axons were visible in every myelinated tract known to arise from immunoreactive cell body groups. In immunopositive soma/dendrites as well as axons, the 5-HT2A receptor appe ared mainly cytoplasmic rather than membrane bound. Even though the dendrit ic labeling was generally stronger than the somatic, it did not extend to d endritic spines in such regions as the cerebral and piriform cortex, the ne ostriatum, or the molecular layer of the cerebellum. Similarly, there were no labeled axon terminals in numerous regions known to be strongly innervat ed by the immunoreactive somata and their axons (e.g., molecular layer of p iriform cortex). It was concluded that the 5-HT2A receptor is mostly intrac ellular and transported in dendrites and axons, but does not reach into den dritic spines or axon terminals. Because it has previously been shown that this serotonin receptor is transported retrogradely as well as anterogradel y, activates intracellular transduction pathways and intervenes in the regu lation of the expression of many genes, it is suggested that one of its mai n functions is to participate in retrograde signaling systems activated by serotonin. (C) 1999 Wiley-Liss, inc.