Long-term adaptive changes induced by serotonergic antidepressant drugs

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.

Keywords::

• 5-hydroxytryptamine
• 5-hydroxytryptamine_1A receptor
• antidepressant
• brain-derived neurotrophic factor
• cyclic adenosine monophosphate response-element-binding protein
• hippocampus
• long-term potentiation
• neuroplasticity