Much excitement about antidepressants, DBI and c-FOS

This article briefly outlines the background and major findings of the research projects in which, together with a number of skilled and enthusiastic collaborators, I was involved at FGIN under the mentorship of the late Dr. Erminio Costa.The topics covered are (ì) our search for an endogenous ligand of the [3H]- imipramine binding site, as an approach to shed light on the still today elusive mechanisms underlying the therapeutic action of antidepressant drugs; (ìì) our attempt to correlate psychopathological states, characterized by dysfunctions of the GABAergic neurotransmission, with an altered brain content of Diazepam binding inhibitor (DBI), a peptide that exerts a direct negative modulation of GABAA receptor function and also, by binding to the mitochondrial benzodiazepine receptor, increases the brain content of GABAA receptor-active neurosteroids; (ììì) our demonstration that the activation of the glutamate/NMDA receptor, throughstimulation of several intracellular signaling pathways, induces the expression of the early inducible gene c-fos, a mechanism proposed to underlie glutamate-mediated neuronal plasticity.