Researcher profile

Sachin Patel

The overall goals of our research are to understand the function of cannabinoid signaling systems at the cellular, synaptic, and circuitlevel, investigate the role of eCBs in the pathophysiology of stress-related and substance use disorders, and elucidate cellular and circuit-mechanisms underlying cannabinoid modulation of emotional behavior. To this end, we identified the eCB 2-arachidonoylglycerol (2-AG) as a key regulator of stress response physiology. We have used genetic, pharmacological, electrophysiological and optogenetic approaches to demonstrate that 2-AG bidirectionally regulates innate avoidance, conditioned fear, fear generalization, and stress susceptibility via modulation of amygdala glutamatergic neurotransmission. These studies have led to a now widely accepted model positing that deficiencies in 2-AG signaling represent a susceptibility endophenotype for the development of stress-related psychiatric disorders and identifying the 2-AG hydrolase monoacylglycerol lipase (MAGL) as a putative target for treatment of stress-related disorders. Broadening potential approaches for manipulating endocannabinoid signaling, my lab was the first to identify COX-2 as a novel eCB metabolic pathway in vivo. We have also made major strides in understanding the circuits upon which 2-AG acts to counteract the adverse behavioral consequences of stress and in the process elucidated basic aspects of synaptic function in amygdala circuits. Finally, we found that inhibition of 2-AG synthesis reduced voluntary alcohol consumption under a variety of motivation states including under compulsive-like drinking conditions and 2-AG augmentation may represent a novel approach to mitigate hyperalgesic states associated with alcohol withdrawal.