Changes in phosphoinositide signalling activity and levels of the alpha subunit of G(q/11) protein in vat brain induced by E-5842, a sigma(1) receptor ligand and potential atypical antipsychotic

Changes in the phosphoinositide (PPI) signal transduction system induced by E-5842, a new sigma(1) (sigma(1)) receptor ligand and potential atypical a ntipsychotic, were studied in the rat frontal cortex, hippocampus and stria tum. Acute treatment with E-5842 increased phospholipase C (PLC) activity i n the striatum and the hippocampus. Chronic treatment with E-5842 induced a n increase in the activity of PLC in the frontal cortex and the striatum. S imilar up-regulation of the activity of the enzyme was also observed in rat frontal cortex membranes in presence of GTP gamma S. After chronic treatme nt with E-5842, it was a Iso observed a significant increase of the im mu n o reactivity levels of G(q/11 alpha) in the frontal cortex. Our results sug gest that part of the antipsychotic effects of E-5842 could be related to t he regulation of the PPI signal transduction pathway, especially after a pr olonged treatment. (C) 2000 Elsevier Science Ireland Ltd. All rights reserv ed.