The Frank lab develops light-sensitive small molecule probes to manipulate neurons with increased spatiotemporal precision. In particular, we focus on developing photo-switchable and photo-caged ligands which permit remote control over cannabinoid receptor (CBR) activity.
The CBRs are widely distributed across the human nervous system and are important to a number of neuropsychological conditions including drug addiction. CB1 and CB2 are inhibitory GPCRs that respond to lipophilic endocannabinoids such as anandamide. They remain infamous due to their activation by Δ9-tetrahydrocannabinol (Δ9-THC), a component of Cannabis sativa believed to exert its psychoactive effects primarily via CB1 in the brain. As consumption of cannabinoids for medicinal or recreational use becomes more widespread, it is critical we investigate their potential to modulate reward processing and addictive behavior. Importantly, we must also understand their interactions with other narcotics like opioids, the abuse of which presents an increasing health epidemic across North America.
Our lab uses a multidisciplinary approach involving organic chemical synthesis, whole-cell electrophysiology, fluorescence imaging and immunohistochemistry to develop and assess the ability of our technology to interface with brain tissue at subcellular precision. After chemical synthesis of the probes, we evaluate their activity in cultured rodent neurons and acute brain slices. These tools are designed to illuminate the roles of CBRs in modulating rewarding stimuli in the mesolimbic dopamine system and will be used probe the interactions between cannabinoid and opiate receptors in models of addiction.