Long-term adaptive changes induced by serotonergic antidepressant drugs.
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.
Faure
Céline
C
Laboratoire 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
Mnie-Filali
Ouissame
O
Haddjeri
Nasser
N
D000223:Adaptation, Psychological / Q000187:drug effects*; D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy; D005104:Expert Testimony; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
D000928:Antidepressive Agents; D018490:Serotonin Agents; D012701:Serotonin