Decrease of adenylyl cyclase activity and expression by a sigma(1) receptor ligand and putative atypical antipsychotic

We examined whether changes in the adenylyl cyclase system could be induced by the administration of the sigma(l) receptor ligand and putative atypica l antipsychotic 4-[4-fluorophenyl]-1,2,3,6-tetrahydro-1-[4-{1,-2,4-triazol- 1-il)butyl]pyridine citrate) (E-5842). Repeated (21 days) but nor. acute (2 h) treatment with E-5842 induced a significant decrease in adenylyl cyclas e type 1 immunoreactivity and adenylyl cyclase activity in rat frontal cort ex membranes, with less or no effect in other brain regions such as the hip pocampus or the striatum. Changes in immunoreactivity were not observed in other adenylyl cyclases (type V/VI). The reported changes, observed only af ter a chronic treatment, could be related to the mechanism of action of sig ma receptor ligands in general or to that of E-5842 in particular and shoul d be taken into account, given the long duration of treatment in psychiatri c patients. NeuroReport 12: 1989-1992 (C) 2001 Lippincott Williams & Wilkin s.