5-HYDROXYTRYPTAMINE(2A) SEROTONIN RECEPTORS IN THE PRIMATE CEREBRAL-CORTEX - POSSIBLE SITE OF ACTION OF HALLUCINOGENIC AND ANTIPSYCHOTIC-DRUGS IN PYRAMIDAL CELL APICAL DENDRITES

To identify the cortical sites where 5-hydroxytryptamine(2A) (5-HT2A) serotonin receptors respond to the action of hallucinogens and atypica l antipsychotic drugs, we have examined the cellular and subcellular d istribution of these receptors in the cerebral cortex of macaque monke ys (with a focus on prefrontal areas) by using light and electron micr oscopic immunocytochemical techniques, 5-HT2A receptor immunoreactivit y was detected in all cortical layers, among which layers II and III a nd layers V and VI were intensely stained, and layer IV was weakly lab eled, The majority of the receptor-labeled cells were pyramidal neuron s and the most intense immunolabeling was consistently confined to the ir parallelly aligned proximal apical dendrites that formed two intens ely stained bands above and below layer IV, In double-label experiment s, 5-HT2A label was found in calbindin D28k-positive, nonphosphorylate d-neurofilament-positive, and immune-negative pyramidal cells, suggest ing that probably all pyramidal cells express 5-HT2A receptors, 5-HT2A label was also found in large-and medium-size interneurons, some of w hich were immune-positive for calbindin, 5-HT2A receptor label was als o associated with axon terminals. These findings reconcile the data on the receptor's cortical physiology and localization by (i) establishi ng that 5-HT2A receptors are located postsynaptically and presynaptica lly, (ii) demonstrating that pyramidal neurons constitute the major 5- HT2A-receptor-expressing Cells in the cortex, and (iii) supporting the view that the apical dendritic field proximal to the pyramidal cell s oma is the ''hot spot'' for 5-HT2A-receptor-mediated physiological act ions relevant to normal and ''psychotic'' functional states of the cer ebral cortex.