Darakhshan Jabeen Haleem.
Serotonergic mechanism of Antidepressant Action and Adaptation to stress.
J Coll Physicians Surg Pak Jan ;9(3):139-46.

Investigations on the mechanism of action of antidepressants suggested that they enhance neurotransmission across monoamine synapse by inhibiting neuronal reuptake or degradation of monoamines. Development and introduction of specific serotonin reuptake inhibitors (SSRIs) was prompted by the desire to eliminate some side effects of traditional antidepressants. These drugs act by selectively inhibiting the neuronal reuptake of 5-hydroxytryptamine (5-HT; serotonin). Theories on the causative agents of depressive symptoms, therefore, focused on the hypoactivity of the monoaminergic and particularly serotonergic systems of the brain. However, a number of points remain unclear. The effects of SSRIs and other antidepressants on serotonin and/or monoamine synapse are immediate whereas clinical improvement may take place some weeks. Several compounds could increase serotonergic/monoaminergic activity but are not antidepressant. Animal studies show that an episode of stress although increases brain 5-HT metabolism but behavioral deficits comparable to a model of depression are produced. On the other hand, increases of brain 5-HT metabolism do not occur in animals adapted to a repeated stress schedule. Recent studies show that long term antidepressant administration as well as adaptation to stress both desensitize 5-HT-1A receptors located on cell soma and/or dendrites of serotonergic neurons. In view of serotonin hypothesis of depression, a fall in the efficacy of negative feedback action at 5-HT synapse would be a possible mechanism of antidepressant action and adaptation to stress.

PakMediNet -Pakistan's largest Database of Pakistani Medical Journals - http://www.pakmedinet.com