DOPAMINE RECEmOR MESSENGER RNA: LOCALIZATION IN THE HUh4AN HIPPOCAMPUS

It is known that there exist specific neurodevelopmental abnormalities in the medial temporal lobe in schizophrenia. For example, pre-a cells in the parahippocampal gyrus show aberrant migration patterns. It is possible that glutamate abnormalities previously shown in schizophrenia are related to neurodevelopment, and the abnormalities seen in dystrophic cells (glutamate receptors have trophic properties). We have previously shown that the expression of a particular glutamate receptor subunit (GluKl) is markedly reduced in schizophrenia (Harrison et al, Lancet 337, p450), and as a test of temporal lobe immaturity in schizophrenia, we have investigated the expression of two developmentally distinct isoforms of the glutamate receptor subunits GluRA and GluRB in the hippocampus of 17 schizophrenics and 13 ageand sex-matched control brains by the techniques of in situ hybridization and quantitative film autoradiography. Initial experiments pointed to the fact that the expression pattern of these isoforms of GluRA and GluRB was different in human hippocampus when compared to the rat, and cloning of cDNA from human frontal cortex has revealed that the two isoforms of human GluRB have virtual nucleotide sequence identity with the alternatively-spliced exons in the rat, confming the usefulness of oligonucleotides complementary to the rat cDNAs as probes for these receptor subunits in human neuropsychiatric disorders. These results suggest that we are able to confirm these sequences as developmentally relevant in human brain tissue and facilitates a post mortem approach to understanding the developmental abnormality in schizophrenia.