α- and α-adrenoceptor expression and functionality in postmortem prefrontal cortex of schizophrenia subjects.

Previous evidence suggests that α-adrenoceptors (α-AR) may be involved in the pathophysiology of schizophrenia. However, postmortem brain studies on α-AR expression and functionality in schizophrenia are scarce. The aim of our work was to evaluate α-AR and α-AR expression in different subcellular fractions of prefrontal cortex postmortem tissue from antipsychotic-free (absence of antipsychotics in blood at the time of death) (n = 12) and antipsychotic-treated (n = 12) subjects with schizophrenia, and matched controls (n = 24). Functional coupling of α-AR to G proteins induced by the agonist UK14304 was also tested. Additionally, G protein expression was also evaluated. In antipsychotic-free schizophrenia subjects, α-AR and α-AR protein expression was similar to controls in all the subcellular fractions. Conversely, in antipsychotic-treated schizophrenia subjects, increased α-AR expression was found in synaptosomal plasma membrane and postsynaptic density (PSD) fractions (+60% and +79% vs controls, respectively) with no significant changes in α-AR. [S]GTPγS SPA experiments showed a significant lower stimulation of G and G proteins by UK14304 in antipsychotic-treated schizophrenia subjects, whereas stimulation in antipsychotic-free schizophrenia subjects remained unchanged. G protein stimulation was significantly decreased in both antipsychotic-free and antipsychotic-treated schizophrenia subjects compared to controls. Expression of G protein did not differ between groups, whereas G levels were increased in PSD of schizophrenia subjects, both antipsychotic-free and antipsychotic-treated. G protein expression was increased in PSD of antipsychotic-treated subjects and in the presynaptic fraction of antipsychotic-free schizophrenia subjects. The present results suggest that antipsychotic treatment is able to modify in opposite directions both the protein expression and the functionality of α-AR in the cortex of schizophrenia patients.