Graduation Year

2014

Document Type

Open Access Senior Thesis

Department

W.M. Keck Science Department

Second Department

Neuroscience

Reader 1

John Krstenansky

Reader 2

Thomas Borowski

Rights Information

© 2014 Rebecca Schell

Abstract

Major depressive disorder affects people’s productivity and ability to function in everyday life. The disorder can be attributed to neurochemical imbalances of various neurotransmitters including but not limited to serotonin, dopamine, and norepinephrine. Conventional pharmacological treatments have focused primarily on these three neurotransmitters, and have been shown to be effective in alleviating most of the major symptoms of depression. Although these treatments are effective with most patients, they are known to have adverse side effects, causing patients to seek alternative treatments. Sceletium tortuosum, a succulent plant found in the Cape region of South Africa, has been shown to have anxiolytic effects when used recreationally. Studies have confirmed the presence of a family of alkaloids mesembrines that are present within the plant and believed to be responsible for the calming effects. Pharmacological analyses have revealed that individual members of the alkaloid family act as either serotonin reuptake inhibitors (SRI) or phosphodiesterase-4 (PDE4) inhibitors. The current study seeks to elucidate the antidepressant properties of the mesembrine alkaloids in a mouse model of depression. Isolated alkaloids were administered at a low dose (10 mg/kg) and a high dose (80 mg/kg) to BALB/c mice in the forced swim test a rodent model of behavioral despair. This was compared with paroxetine (Paxil) (1 mg/kg), a selective serotonin reuptake inhibitor with proven antidepressant efficacy, and 0.9% saline. Each trial of the forced swim test was administered for six minutes and the duration of swimming and immobility was measured. In order to assess any locomotor effects of the drug treatments, an open field exploration test was also employed one week following the forced swim task. Results from the forced swim test revealed a statistically significant reduction in the duration of immobility (behavioral despair) between the low dose of alkaloids and saline. No significant effects in immobility were found across the other drug treatment conditions (high dose mesembrine, paroxetine, and saline). Further, none of the treatment groups showed statistically significant locomotor interference effects in the open field exploration test. We conclude that the mesembrine alkaloids present in Sceletium tortuosum have antidepressant properties and may represent a suitable alternative for the treatment of major depressive disorder.

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