Changes in serotonin(2A) and GABA(A) receptors in schizophrenia: Studies on the human dorsolateral prefrontal cortex

Having shown a decrease in serotonin(2A) receptors in the dorsolateral pref rontal cortex (DLPFC) from schizophrenic subjects, we have now determined i f this change was reflective of widespread changes in neurochemical markers in DLPFC in schizophrenia. In Brodmann's area (BA)9 from 19 schizophrenic and 19 control subjects, we confirmed a decrease in the density of [H-3]ket anserin binding to serotonin(2A) receptors in tissue from the schizophrenic subjects [39 +/- 3.3 vs. 60 +/- 3.6 fmol/mg estimated tissue equivalents ( ETE); p < 0.005], In addition, the density of [H-3]muscimol binding to GABA , receptors was increased in the schizophrenic subjects (526 +/- 19 vs. 444 +/- 28 fmol/mg ETE; p < 0.02), [H-3]YM-09151-2, N-[1-(2-thienyl)cyclohexyl ]-3,4-[H-3]piperidine, PH]SCH 23390, [H-3]mazindol, and N-G-nitro-L-[H-3]ar ginine binding to BA 9 did not differ between groups, and there was no spec ific binding of [H-3]raclo-pride or 7-hydroxy-2-(di-n-[H-3]propylamino)tetr alin to BA 9 from either cohort of subjects. This suggests the density of d opamine D-1-like and NMDA receptors, the dopamine transporter, and nitric o xide synthase activity are not altered in BA 9 from schizophrenic subjects. The selective nature of the changes in serotonin(2A) and GABA, receptors i n DLPFC could indicate that these changes are involved in the pathology of schizophrenia.