The effect of long-term administration of imipramine (10 mg/kg po, twice daily, 30 days) with or without nifedipine (5 mg/kg ip, twice daily, 28 days) on the G protein alfa subunit, Gs-alfa, Go-alfa and Gi-alfa mRNA levels was investigated in the rat hippocampus. An in situ hybridization histochemistry showed that imipramine decreased the Go-alfa mRNA level in CA1 (by ca. 40%) and CA3 (by ca. 37%) hippocampal fields and, to a lesser extent, in the dentate gyrus (by ca. 25%), but had no effect on the Gs-alfa and Gi-alfa mRNA levels in those structures. Nifedipine decreased (by ca. 30%) the Gs-alfa level in the studied fields of hippocampal formation, having no imfluence on the level of mRNA which codes other subunits of G protein, Coadministration of nifedipine and imipramine reversed the imipramine effect on Go-alfa, but had no effect on the nifedipine induced decrease at the Gs-alfa mRNA level. These results suggest that inhibition of L calcium channels modifies the effect of imipramine at the level of intracellular signal transduction.