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Completed Research Projects
Title: Interoceptive Stressor Conditioning: A Model for Gulf War Illness
Synopsis: This animal study compared the relationship between reflexes and learned responses after PB had been given.
Overall Summary: The cause of Gulf War Illness (a broad category for unexplained symptom development that includes headaches, rashes, chronic fatigue, joint pain, memory and concentration problems) is still unknown. We have developed an animal model that can serve to discern the causal relationship between internal feelings (which we view as an interoceptive stressors) and contextual learning. The model suggests that the initial symptom development occurs through associative learning (Pavlovian conditioning) between interoceptive stressors (e.g. side effects from pyridostigmine bromide (PB), vaccinations, etc) and contextual stimuli. As conditioned response occur with the recurrent presentation of those contextual stimuli, the unknown origin of the perceived symptoms (conditioned responses) lead to further conditioning of symptoms to additional contextual stimuli (higher-order conditioning). Through higher-order conditioning causes of the "illness" can perpetuate, increase in scope, and appear totally different in form from the initial unconditional stimuli (the initial cause of symptoms).
Overall Project Objective: To understand the relationship between the unconditional responses following PB administration (i.p.) and the elicited conditional responses that occur thereafter.
Results to Date: None to date.
Project: VA-106
Agency: Department Of Veterans Affairs
Location: VAMC East Orange
P.I. Name: K D Beck
Status: Complete
Study Start Date: October 01, 2004
Estimated Completion Date: September 30, 2006
Specific Aims: In study 1, we will determine if the interoceptive stress from PB is occurring through muscarinic or nicotinic receptors and if signaling through the vagus nerve to the brain is necessary for the development of conditioned responses. In the second study, we will measure several physiological parameters to delineate the scope of the conditional responses (nausea, sympathetic/parasympathetic tone, and algesia/analgesia). Study 3 will test whether extinction or counter-conditioning can reduce the appearance of the conditioned responses.
June 2005: The investigator has amendment the study to add experiments that will test whether pharmacologically induced anxiety perpetuate or facilitate the learned illness responses. Also whether the sex of the individual is crucial to the development of conditioned symptoms.
Methodology: The plan of this pilot program is to understand the relationship between the unconditional responses following PB administration (i.p.) and the elicited conditional responses that occur thereafter. Odors will serve as the conditional contextual stimuli. Testing for conditional responses will occur 1-2 weeks after the initial co-occurrence of the PB symptoms and the contextual odor. This research program predominantly requires the measurement of the ASR (using a force plate) in response to brief white noise (0.5 s, immediate rise/fall). Additional measurements include RIA for measuring oxytocin (nausea index), ECG for measuring sympathetic/parasympathetic tone, and paw-lick testing of hot-plate responsivity. In most cases, rats are treated with PB in the presence of a specific odor. Several days later we will measure the conditioned responses that occur when the odor is presented to the rat again (without PB). We have already documented the rats exhibit an exaggerated startle response to the odor days after the initial pairing of the odor and PB. Thus, we will use these various methods to understand the physiological responses the odor elicits in the rat when presented with the odor conditional stimulus. All experiments implement factorial designs. Thus, all experiments will use analysis of variance (ANOVA) to determine differences across treatment conditions.
Publications:
No Publications at this time...
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