Document Type

Honors Paper

Publication Date



Major Depressive Disorder (MDD) accounts for approximately 10% of all diagnosed chronic illness in the United States. The most common treatments for MDD is serotonergic manipulation via pharmacological treatments such as monoamine oxidase inhibitors (MAO-I) or selective serotonin reuptake inhibitors (SSRI). However, not only have these treatments proven to be ineffective for a portion of the population, but they also fail to treat some of the physiological damages that occur in the hippocampus during MDD due to over-activation of inflammatory cells known as microglia. Activation of the CB2 receptor in the hippocampus has been shown to inhibit microglial cells and promote neuron proliferation. This study investigates the effects of the CB2 agonist GW405833 on rats in the chronic mild stress model for depression. Results showed significant decrease in depressive-like behavior in the Forced Swim Test, the Open Field Test for anxiety and the Morris Water Maze. Sucrose Preference testing and weight gain did not differ significantly. Immunohistochemical staining for activated microglial cells and neuron nuclei was performed. The data suggest that CB2 activation could play an important role in MDD treatment for both behavioral and physical changes occurring in the brain.



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