Molecular mechanisms of neuroplasticity and pharmacological implications: the example of tianeptine

The hippocampal formation, which expresses high levels of adrenal steroid receptors, is a malleable brain structure that is important for certain types of learning and memory. This structure is also vulnerable to the effects of stress hormones which have been reported to be increased in depressed patients, particularly those with severe depression. The amygdala, a structure that plays a critical role in fear learning, is also an important target of anxiety and stress. Certain animal models of depression involve application of repeated stress. Repeated stress promotes behavioral changes that can be associated with these two brain structures such as impairment of hippocarnpus-dependent memory and enhancement of fear and aggression, which are likely to reflect amygdala function. At a cellular level, opposite responses in the hippocampus and amygdala are observed, namely, shrinkage of dendrites in hippocampus and growth of dendrites in the lateral amygala, involving in both cases a remodeling of dendrites. Furthermore, stress-induced suppression of neurogenesis has been noted in dentate gyrus. At a molecular level, the effects of repeated stress in the hippocampus involve excitatory amino acids and the induction of the glial form of the glutamate transporter. Chronic treatment with the antidepressant tianeptine may prevent these effects in hippocampus and amygdala. (C) 2004 Elsevier B.V. and ECNP. All rights reserved.