Antidepressants increase CREB-phosphorylation via the 5-HT(1A)-receptor

Neuroplasticity has become a well recognized concept in major depression. In this concept the cyclic AMP-response element binding protein (CREB) as an activity-dependent transcription factor important for synaptic plasticity and memory storage is a key element (1). It has been shown that antidepressants are increasing the phosphorylation of CREB and therefore leading to an increase in neuroplasticity. We have previously demonstrated that fluoxetine and imipramine modulate CREB-phosphorylation in lymphocytic cells the same way as they do in neurons (2). To get further insight which signal transduction pathways are involved we tested the monocyclics alaproclate and fluoxetine, the bicyclic nitroquipazine and the tricyclic imipramine. All these substances equally induced CREB-phosphorylation. This effect was inhibited by the 5-HT(1A) antagonist WAY 100635 but not the 5-HT(2A) antagonist ketanserin. This suggests that SSRIs increase CREB-phosphorylation via the 5-HT(1A)-receptor. This might be the essential signal transduction pathway that mediates the effects of SSRI on CREB-phosphorylation.

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