In addition to morphological deficits, stress-induction paradigms also affect neurotrophin secretion by astrocytes. Social defeat stress reduces GFAP expression (Araya-Callis et al. 2012); this effect is not reversed by citalopram, but is partially rescued by brain-derived neurotrophic factor (Ye et al. 2011). Central inhibition of astrocyte glutamate reuptake by the EAAT2/GLT-1 inhibitor dihydrokainic acid impairs reward processing and hippocampal-dependent spatial working memory, which correlates with anhedonia-like and cognitive-like symptoms, respectively (Bechtholt-Gompf et al. 2010). The anhedonia-like phenotype could be replicated by dihydrokainic acid injection into the PFC alone (John et al. 2012). In addition, PFC astrocyte ablation by the toxin l-alpha-amino-adipic acid results in despair-like behaviours (Banasr et al. 2008). In contrast, the excito-neurotoxin ibotenate has no effect in depressogenic behavioural paradigms, suggesting that gliotoxicity may be more important than neuronal cell death in rodent despair (Banasr et al. 2008).
