Molecular Mechanisms and Applications of a Reserpine-Induced Rodent Model

Abstract

Reserpine, an indole alkaloid isolated from the Rauwolfia serpentina has been around since the 1950s. This compound, used for hypertension treatment, had undesirable side effects in patients. The most notable side effect is the induction of depression. Reserpine works by binding irreversibly to the VMAT2 receptor on biogenic amine storage vesicles. This, in turn, causes the storage vesicles to leak their contents into the neuronal cytosol. Cytosolic enzymes such as monoamine oxidases then catabolize and degrade neurotransmitters including Serotonin (5-HT), Dopamine (DA), and Norepinephrine (NE). The depletion of these biogenic amines leads to an increase in depressive-like behavior in various rodents. In addition to the induction of a depressive state, traits associated with pain were also observed in rodent models. Pain is an important characteristic that is co-morbid in patients with major depressive disorder and often referred as the pain-depression dyad. The extent of the induced-depressive state can be determined by several proven tests such as the forced swimming test, open field test, and mechanical allodynia test. Reserpine also induced visible and empirical changes in rodent behavior such as akinesia, ptosis, and hypothermia to name a few. Current researches utilizing reserpine ranging from drug discovery to pathogenesis of diseases such as fibromyalgia are also summarized. Reserpine has been proved the efficacy as a suitable inducer for depression animal model to further the studies at the molecular and systemic levels.