The Molecular Mechanisms and the Applications of 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 of inducing depression. Reserpine’s action is that it binds 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, in turn, catabolize neurotransmitters, namely 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 inducing a depressive state, traits associated with pain were also observed in rodent models. Pain is an important characteristic that is comorbid in patients with major depressive disorder, often referred to as the pain-depression dyad. The extent of the induced-depressive state can be determined based on several proven tests such as the forced swimming test, open field test, and von Frey Hair test. Reserpine also induced visible and empirical changes in rodent behavior such as akinesia, ptosis, and hypothermia to name a few. Current research utilizing Reserpine ranging from drug discovery to pathogenesis of diseases such as fibromyalgia are also summarized. Reserpine shows efficacy as a suitable model of depression in rodents to further the study of this dis