DOPAMINE D-1 RECEPTOR, D-2 RECEPTOR, PROENKEPHALIN-A AND SUBSTANCE-P GENE-EXPRESSION IN THE CAUDATE-NUCLEUS OF CONTROL AND SCHIZOPHRENIC TISSUE - A QUANTITATIVE CELLULAR IN-SITU HYBRIDIZATION STUDY

The cellular expression of the mRNAs encoding the dopamine D-1 recepto r, dopamine D-2 receptor and the neuropeptides enkephalin and substanc e P was determined in fresh frozen sections of human post-mortem cauda te nucleus from control and schizophrenic brains using the technique o f radioactive in situ hybridisation coupled with computer-assisted ima ge analysis. Measurements of silver grain densities and mean cross-sec tional somatic areas revealed no significant differences in the expres sion of any of these four gene transcripts. Further, cell count estima tes revealed that each of these four mRNAs was expressed by approximat ely 20% of caudate cells (neurones and glia) in both control and schiz ophrenic tissue. These data demonstrate that the cellular expression o f the dopamine D-1 and D-2 receptors and the neuropeptides enkephalin and substance P mRNAs are stable post mortem and that the relative cel lular abundance of these mRNAs is not altered in the caudate nucleus o f schizophrenic brains when compared to controls. These findings draw into focus the possible sites of action of clinically prescribed neuro leptics and suggest that chronic neuroleptic treatment of patients dis playing negative schizophrenic symptoms may 're-set' an underlying neu rochemical imbalance within the caudate nucleus.