Expression of serotonin 5‐HT2A receptors in the human cerebellum and alterations in schizophrenia

Abstract

The occurrence of human cerebellar serotonin 5‐HT_2A receptors (5‐HT_2AR) is equivocal and their status in schizophrenia unknown. Using a range of techniques, we investigated cerebellar 5‐HT_2AR 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 [³H]ketanserin revealed cerebellar 5‐HT_2AR binding sites present at levels approximately a third of that in prefrontal cortex. 5‐HT_2AR mRNA was detected by reverse transcriptase‐polymerase chain reaction, with higher relative levels in men than women. Several aspects of 5‐HT_2AR expression were altered in schizophrenia. 5‐HT_2AR immunoreactivity in Purkinje cells was partially redistributed from soma to dendrites and was increased in white matter. 5‐HT_2AR mRNA was decreased in the male patients. 5‐HT_2AR measured by dot blots and [³H]ketanserin binding (B_max and K_d) were not significantly altered in schizophrenia. These data show that 5‐HT_2AR gene products (mRNA, protein, binding sites) are expressed in the human cerebellum at nonnegligible levels; this bears upon 5‐HT_2AR imaging studies which use the cerebellum as a reference region. 5‐HT_2AR expression is altered in schizophrenia; the shift of 5‐HT_2AR 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.