Impact of natural biologics on the stress response: relationship between fear and appetitive brain circuits

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Specific objectives: While stressors and other highly salient stimuli provoke a wide range of hormonal neurotransmitter and behavioral responses, the underlying triggering mechanisms remain unclear. Increased attention is being focused on the role of several peptidergic systems, in the mediation of these behavioral and physiological responses and in the quest for biologics capable of mitigating those responses. In keeping with our long-term research program, the proposed studies will address the following contentions, initially focused on stressors and then to other biologically salient events: 1. BBs and CRF serve as CNS regulators with integrative properties coordinating the organism's neuroendocrine and behavioral responses to stressors. 2. Stressor exposure will impact motivational and/or emotional states in a variable fashion depending on the type of stressor employed. 3. A systemic challenge (or stressor, e.g. bacterial endotoxin, LPS) will provoke behavioral and neurochemical alterations reminiscent of those elicited by psychogenic stressors. 4. Exposure to an appetitive stimulus will activate some of the same peptidegic circuits as those activated by a aversive stimuli. 5. The effects of these aversive or appetitive events will be attenuated by specific plant-derived biologics, including active ingredients from the neotropical vine Souroubea Symptata Gilgi, and marijuana plant extracts (THC, CBD and/or the terpenes), through their action(s) on BBs and CRF system(s).