The most commonly prescribed treatments for anxiety are benzodiazepines and antidepressants. These therapeutic agents have very different mechanisms of action, time course of effect and side effect profiles. Benzodiazepines enhance the responsiveness of GABA, the major inhibitor neurotransmitter in the brain, by binding to the GABA/benzodiazepine (GABA/BZ) receptor complex. This results in rapid anxiolytic activity in rodent models and in humans, but can be accompanied by sedation. Antidepressants most often used for anxiety include the serotonin selective reuptake inhibitors (SSRIs), which block the serotonin (5-HT) transporter and increase synaptic levels of this monoamine. However, the therapeutic action of antidepressants for the treatment of anxiety, as well as depression, requires several weeks and sometimes months. This has led to the widely held hypothesis that adaptations, or neural plasticity changes, to the acute elevation of 5-HT are necessary for a therapeutic effect. Because of this hypothesis, there has been a great deal of research directed toward identification of the molecular and cellular adaptations to repeated antidepressant treatment. In contrast, there is much less known about the intracellular signaling that is relevant to the actions of benzodiazepines. This section will discuss the signaling adaptations resulting from antidepressants, as well as benzodiazepines. These effects will be discussed with regard to the signaling pathways regulated by fear and stress.
Was this article helpful?