It Takes Two to Tango: Investigating the Relationship between Ghrelin and Endocannabinoids within the Ventral Tegmental Area with Regards to Feeding

Ghrelin is a hormone that targets the brain to increase food intake and energy balance. Recent evidence suggests that ghrelin increases appetite in part by acting on growth hormone secretagogue receptors (GHSR) in the ventral tegmental area (VTA), a brain region associated with reward seeking behaviors. The ability of ghrelin to induce appetite is reminiscent of the appetite inducing effects of endogenous cannabinoids (CBs). Interestingly, ghrelin’s ability to stimulate feeding within the hypothalamus is dependent on a functional CB system within this region. In the present thesis we hypothesized that ghrelin and CB systems work in tandem within the VTA to stimulate feeding. Here we showed that ghrelin significantly increased food intake (p < .05) when directly microinjected into the VTA of rats. Furthermore, we demonstrated that this corresponding increase in food intake depended on a functional endocannabinoid system as peripheral pre-treatment with a selective CB-1 receptor (CB-1R) antagonist (i.e. rimonabant) completely attenuated this increase in food intake to control rat levels. Furthermore, we also demonstrated via reverse transcription quantitative polymerase chain reaction (RT-qPCR) experiments that CB-1R mRNA expression is significantly lower in the VTA but enhanced in the prefrontal cortex (PFC) of GHSR knock-out (GHSR KO) relative to wildtype (WT) rats (p < .05). Together, these data provide evidence that ghrelin targets the VTA to increase food intake through a mechanism that requires a functional endocannabinoid system.