Stress, chemical defense agents, and cholinergic receptors. Midterm report, 1 November 1987-31 July 1989
This project is assessing the affects of exposure to a chemical defense agent on anxiety and stress, by using rat models of anxiety (conditioned emotional response (CER); conditioned suppression) and unconditioned non-specific stres (exposure to footshock). The specific experiments determined the plasticity of muscarinic cholinergic binding sites in the central nervous system. The neuroanatomical locus and neuropharmacological profile of changes in binding sites were assessed in brain areas enriched in cholinergic markers. Acetylcholine turnover was measured to determine if the receptor response is compensatory or independent. The effects of acute exposure to doses of a chemical defense agent (soman--XGD) on lethality and behaviors were examined. The experiments involved training and conditioning adult rats to CER using standard operant/respondent techniques. The binding of radiolabelled ligand was studied in vitro using brain membranes and tissue sections (autoradiography). The major findings are that CER produces increases in acetylcholine turnover in brain areas involved in anxiety, and that primarily post-synaptic M1 receptors compensatorly decrease in response. These neurochemical phenomena are directly correlated with several behaviors, including onset and extinction of CER and non-specific stress. Followup experiments have been designed to test the interaction of CER, XGD and neurochemistry.
- Research Organization:
- Texas Coll. of Osteopathic Medicine, Fort Worth, TX (USA). Dept. of Pharmacology
- OSTI ID:
- 6004465
- Report Number(s):
- AD-A-228336/4/XAB; CNN: DAMD17-88-C-8026
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEFENSE
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
RECEPTORS
CHEMICAL WARFARE AGENTS
BIOLOGICAL EFFECTS
ACUTE EXPOSURE
AUTORADIOGRAPHY
BEHAVIOR
BIOLOGICAL MARKERS
BIOLOGICAL STRESS
BRAIN
CELL MEMBRANES
METABOLISM
PROGRESS REPORT
RADIOISOTOPES
RATS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DOCUMENT TYPES
DRUGS
ESTERS
ISOTOPES
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PROTEINS
QUATERNARY COMPOUNDS
RODENTS
VERTEBRATES
WEAPONS
560300* - Chemicals Metabolism & Toxicology
450600 - Military Technology
Weaponry
& National Defense- Chemical & Biological- (1990)
550501 - Metabolism- Tracer Techniques