Astrocytes secrete many neurotrophins in response to antidepressants; amitriptyline increases basic fibroblast growth factor (FGF-2/bFGF) mRNA expression in astrocyte but not neuronal primary cultures. In the learned helplessness model, imipramine’s effects were attenuated by fluorocitrate (a reversible astrocyte inhibitor) into the hippocampal CA3/dentate gyrus (Iwata et al. 2011). Intracere-broventricular and intra-PFC infusion of FGF-2/ bFGF reverses anhedonia-like behaviours, and this effect can be blocked by infusion of a specific FGF receptor antagonist (Elsayed et al. 2012). As a result, glial-derived neurotrophins are both necessary and sufficient for antidepressant efficacy in rodent models of depression.
