3rd Annual Academic Symposium - Monica Danala

Depression is a common mental illness associated with the mood catacholemine theory. Many antidepressants are available in the market like selective serotonin reuptake inhibitors (SSRIs) and Monoamine oxygenase inhibitors (MOAIs). However, they exert their mood elevating effects only after several weeks to months of administration. Previous studies suggested that cannabinoids at low doses are potent antidepressants and the action is mediated through CB1 receptors. The antidepressant activity of cannabinoids was paralleled by an increased activity in the neurons that produce serotonin.
I propose investigating the role of ß-arrestin2 in regulating the ligand-stimulated CB1 receptor, activating the Mitogen activated protein kinase (MAPK) cascade and thereby eliciting antidepressant activity. The hypothesis of my study is that ‘Anti-depressant effects of Cannabinoid drugs on CB1 receptors are mediated through ß-arrestin2 binding to the receptor, its desensitization and activation of the MAPK cascade, thereby elevating phospho-ERK1/2 levels in the hippocampal and prefrontal cortex region of C57BL/6 ßarrestin2 wild-type mice’.
ß-arrestin2 wildtype and knockout mice will be used in this study. Cannabinoids: Δ9 tetrahydrocannabinol (2.5mg/kg), CP55940 (0.06mg/kg), 2-Arachidonoyl glycerol (3mg/kg) and SR141716A (3mg/kg) along with a vehicle control will be initially evaluated in the spontaneous activity assay in WT mice to see if the doses affect locomotor activity. Forced swimming test (FST) and tail suspension test (TST) will be used todetermine the antidepressant activity of the drugs with acute treatment. This will be followed by brain isolation studies involving western blots to determine the relative amounts of phospho-ERK in wildtype and knockout mice. Data will be analyzed by two-way ANOVA following a post-hoc test, comparing treatments with the vehicle and comparing treatments between the genotypes.
Understanding the mechanism could contribute in providing stronger evidence to prove the potential of cannabinoids as antidepressants and development of new psychoactive drugs.