Neurogenesis-dependent and -indepe ... | Article | H1 Connect

There is an element of preternatural to the concept of an animal model of depression, as the melancholic mouse will fail to effectively communicate how the therapeutic intervention has lifted its mood. However, rodents and humans undergo certain similar physiological changes during the onset of anxiety and depressive-like disorders and one of them consists of altered hypothalamo-pituitary-adrenal axis activity, resulting in higher plasma levels of glucocorticoids. With a view to develop a new model of depression and further unravel the molecular mechanisms of antidepressant action, David et al. simply supplemented the drinking water of their mice with corticosterone and observed an increase in depressive-like behaviour; this effect was reversed by treatment with two classical antidepressants, fluoxetine and imipramine. Crucially, the effects of fluoxetine were shown to be mediated by mechanisms both dependent on and independent on hippocampal neurogenesis, adding to the exciting debate about the substrate for this drug’s action. Further microarray work, complemented with the use of transgenic mice, revealed that fluoxetine acts by affecting beta-arrestin 2, a protein involved in the internalisation of G-protein-coupled receptors. A question remains: is this chronic corticosterone mouse model relevant to human psychological health? Nevertheless, this work offers great insights into the mechanisms of antidepressant action and should provide a platform for the design and screening of future therapeutic compounds. This makes fascinating reading, even for the non-animist sceptics.