CRH and Anxiety: This extrahypothalamic CRF is known to activate neural circuits involved in stress-induced anxiety, aversion, and reinstatement of drug-seeking behavior, independent of HPA activation.57, 58, 59, 60 Although numerous questions remain regarding how CRF interacts with the noradrenergic system, many studies have reported exciting developments regarding the inputs providing CRF to the LC, the effects of endogenous and exogenous CRF on LC neuron physiology, and the role of LC CRF in mediating anxiety- and stress-related behaviors.