Project Details for

Completed Research Projects

Title: Interactions Between Maternal Care, Stress and Pyridostigmine Bromide
Synopsis: This animal study tested the effects of stress and pyriodstigmine bromide on rats.
Overall Summary: After the first Gulf War, an extraordinarily large number of veterans registered nonspecific complaints of an unknown etiology, which has come to be known as Gulf War Illness. Among the unique conditions affecting troops was the use of pyridostigmine bromide (PB), a pretreatment in case of potential nerve gas exposure. While generally regarded as safe, PB may produce untoward consequences in particularily vulnerable individuals. Vulnerability has two primary sources: genetic variation (ie. altered scavenger activity) and experiential (ie. altered stress reactivity). Accordingly, childhood trauma or abuse effects future stress responses in adults (Heim et al. 2002) which can be modeled in rodents through alterations in maternal care. Bidirectional stress responses are obtained through manipulating the amount of maternal care by separating mothers from pups for varying amounts of time. Separating litters from their mothers for 15 minutes/day for the first two weeks of life (H) induces increased licking and grooming (LG) of offspring that leads to dampened hypothalamic-pituitary-adrenal (HPA) responses to stressors in adult offspring. Increasing the duration of separation to 180 minutes (MS) results in decreased LG and exaggerated HPA responses to stressors in adult offspring (Liu et al. 1997; Weaver and Meaney 1997). In a preliminary study MS rat given an acute dose of .5 mg/kg PB had a significant increase (p <0.05) in acoustic startle response (ASR) both 1 and 15 days after PB treatment. ASRs were not affected by PB in H rats. We are hypothesizing that differential stress responses to the peripheral effects of PB drives the vulnerability to PB found in the MS rat and the immunity to PB found in the H rat.
Overall Project Objective: Our objectives are to measure both central and peripheral cholinergic and stress responses to PB in MS and H rats. Our goal is to determine the relative importance of stress reactivity and/or cholinergic responses to PB in producing the vulnerability to PB detected in MS rats.
Results to Date: None to date.
Project: VA-123
Agency: Department Of Veterans Affairs
Location: VAMC East Orange
P.I. Name: Shelley Weaver
Status: Complete
Study Start Date: October 01, 2004
Estimated Completion Date: September 30, 2007
Specific Aims: The proposed set of studies, working towards the development of an independent research program, are aimed at determining how early life experiences can lead to vulnerabilities to mass treatment regimens in adults. Accounting for such vulnerabilities will lead to better mass treatment regimens, ultimately reducing the number of veterans developing unexplained illness after wartime service.
Methodology: We will generate MS and H Long-Evans rats through repeated daily separation of litters from mothers for 15 or 180 minutes per day for the first two weeks of life. Adult rats will be given 0.5 mg/kg PB i.p., or an equal volume of saline, and housed for 1 hour in either the ASR testing apparatus, a novel environment, or their home cage to determine the importance of novelty and/or context in PB-induced increases in ASR in MS rats. The subsequent study will involve an exploration of differences in cholinergic stimulation in response to PB in MS and H rats via measurements of plasma BuChE activity and brain region specific AChE activity both within and external to the blood brain barrier. We will then examine the HPA response to PB via repeated blood sampling and measurement of plasma corticosterone and ACTH concentrations. Finally, we will measure mRNA expression for c-fos in brain regions involved in stress responses, and peripheral afferent signaling arising from the gastrointestinal tract.
Publications:
No Publications at this time...