Neuritogenesis, a neuroadaptive mechanism of antidepressant drugs action

Newsletter # 49

Cellular models

Today, growing interest has shifted to the reactivation of a juvenile-like plasticity in the brain for the treatment of depression. The reason of this new focus comes from the inability of monoamine oxidase inhibitors and tricyclic antidepressants to rapidly improve depression symptoms. Indeed, despite the fast elevation of monoamine, symptom improvement occurs only after several weeks. This delayed onset suggests that progressive changes in the brain, such as axonal sprouting and the formation of new synapses are neuroadaptive response to antidepressant.

To be in line with this development concept, NEUROFIT proposes neuronal neurite outgrowth assay to demonstrate the effect of your antidepressant compounds on neuronal plasticity. Our data indicate that enhancement of neurite outgrowth is a common feature of current antidepressant drugs on the market.

  • Amitriptyline (Elavil) and Imipramine (Tofranil or Melipramine) are tricyclic antidepressant (TCA) used to treat major depressive disorders.

  • Both are very effective at promoting neurite growth (up to 65%).

  • Fluoxetine (Prozac or Sarafem), a selective serotonin reuptake inhibitor (SSRI) is the most prescribed class of antidepressant.

    Fluoxetine dose-dependently increases by up to 80% the neurite growth in cortical neurons.

  • Venlafaxine (Effexor, Lanvexin, Viepax or Trevilor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class.

    Venlafaxine significantly promotes neurite outgrowth in a dose-dependent manner but in a lesser extent than SSRI or TCA.

  • Reboxetine (Endronax or Prolift), a norepinephrine reuptake inhibitor (NRI) used to treat unipolar depression.

    Reboxetine promotes significant neurite growth although the effective concentration window is narrowed by side effect observed beyond 5µM.

NEUROFIT offers a range of validated in vitro and in vivo screening tests for psychiatry and neurology.

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