[Molecular aspects of antidepressive therapy. Transsynaptic effects on signal transduction, gene expression and neuronal plasticity].
Simple neurotransmitter theories cannot sufficiently explain the mode of action of antidepressant drugs. Molecular pharmacological studies demonstrate that antidepressive treatment initially modulates the neurotransmitter-receptor interaction, subsequently influences signal transduction cascades beyond the synapse and gene transcription mechanisms, and ultimately triggers the expression of specific target genes. Such genes often code for molecules which play an important role in the maintenance of neural and synaptic plasticity. Chronic (but not acute) treatment with antidepressants modulates, for example, the cAMP-second-messenger system and increases the expression of neurotrophic factors. Furthermore, antidepressants promote hippocampal neurogenesis. Stress, an important risk factor for psychiatric disorders, often induces opposite effects. A better understanding of the molecular and cellular effects of stress and therapy with psychotropic drugs will stimulate the development of innovative treatment strategies for which an optimised antidepressant efficacy with a simultaneously improved tolerance is expected.
Thome
J
J
Biochemisches Labor, Zentralinstitut für Seelische Gesundheit, Mannheim.thome@zi-mannheimde
Duman
R S
RS
Henn
F A
FA
D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009414:Nerve Growth Factors / Q000235:genetics*; D018377:Neurotransmitter Agents / Q000235:genetics*; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
D000928:Antidepressive Agents; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter