Expression of serotonin 5‐HT 2A receptors in the human cerebellum and alterations in schizophrenia

The occurrence of human cerebellar serotonin 5‐HT 2A receptors (5‐HT 2A R) is equivocal and their status in schizophrenia unknown. Using a range of techniques, we investigated cerebellar 5‐HT 2A R expression in 16 healthy subjects and 16 subjects with schizophrenia. Immunocytochemistry with a monoclonal antibody showed labelling of Purkinje cell bodies and dendrites, as well as putative astrocytes. Western blots showed a major band at ∼45 kDa. Receptor autoradiography and homogenate binding with [ 3 H]ketanserin revealed cerebellar 5‐HT 2A R binding sites present at levels approximately a third of that in prefrontal cortex. 5‐HT 2A R mRNA was detected by reverse transcriptase‐polymerase chain reaction, with higher relative levels in men than women. Several aspects of 5‐HT 2A R expression were altered in schizophrenia. 5‐HT 2A R immunoreactivity in Purkinje cells was partially redistributed from soma to dendrites and was increased in white matter. 5‐HT 2A R mRNA was decreased in the male patients. 5‐HT 2A R measured by dot blots and [ 3 H]ketanserin binding (B max and K d ) were not significantly altered in schizophrenia. These data show that 5‐HT 2A R gene products (mRNA, protein, binding sites) are expressed in the human cerebellum at nonnegligible levels; this bears upon 5‐HT 2A R imaging studies which use the cerebellum as a reference region. 5‐HT 2A R expression is altered in schizophrenia; the shift of 5‐HT 2A R from soma to dendrites is noteworthy since atypical antipsychotics have the opposite effect. Finally, the results emphasise that expression of a receptor gene is a mutifaceted process. Measurement of multiple parameters is necessary to give a clear picture of the normal situation and to show the profile of alterations in a disease. Synapse 42:104–114, 2001. © 2001 Wiley‐Liss, Inc.