Long-term adaptive changes induced by serotonergic antidepressant drugs
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Updated: Aug 11, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
Céline Faure1, Ouissame Mnie-Filali, Nasser Haddjeri
1Laboratoire de Neuropharmacologie et Neurochimie, Faculté de Pharmacie, Université Claude Bernard, Lyon 1, EA-512, 8, Avenue Rockefeller, 69373 Lyon Cedex 08, France. cfaure@sante.univ-lyon1.fr
Abstract:
The development of conventional antidepressants has been largely based on the hypothesis of monoaminergic dysfunctions and focuses particularly on the serotonin 5-hydroxytryptamine (5-HT) system. Hence, various classes of antidepressant treatments enhance 5-HT neurotransmission with a time course consistent with their delayed therapeutic effect. This delayed onset appears to be associated with the gradual development of specific adaptive changes of functional 5-HT receptors. However, recent theories suggest that major depressive disorders may be associated with impairments of functional plasticity and cellular flexibility. This review discusses several physiological mechanisms by which 5-HT function and hippocampal neuroplasticity are regulated. Knowledge of these long-term adaptations will increase not only our understanding of pathological processes underlying affective disorders, but could also lead to the development of new strategies to treat these devastating illnesses.
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