title: Repeat exposure to ciguatoxin leads to enhanced and sustained thermoregulatory, pain threshold and motor activity responses in mice: relationship to blood ciguatoxin concentrations.
abstract: Ciguatera is a common illness in tropical and subtropical regions that manifests in complex and long-lived symptoms which are more severe in subsequent exposures. This study measures central and peripheral neurologic signs, in parallel with blood toxin levels, in mice exposed once or twice (at 3 days interval) to a sublethal dose of ciguatoxin P-CTX-1 (0.26ng/g via i.p.). Mice were implanted with radiotransmitters to monitor motor activity and core temperature. A single exposure to ciguatoxin elicited an immediate and transient decrease in motor activity and temperature, and subsequent long-lasting thermoregulatory dysfunction resulting in stabilized body temperature around 36.0 degrees C with no observable circadian rhythm. The hypothermic response and the reduced activity were enhanced with a second exposure with 30% of the mice dying within 7h. Measurement of the peripheral nervous system by the tail flick assay revealed increased latency with a single ciguatoxin exposure, and a greater effect following the second exposure. Toxin was measurable in blood up to 3 days following the first exposure; at the 1h time point the concentrations were significantly elevated after a second exposure. These findings indicate an early response to ciguatoxin manifest in a central response to lower body temperature and reduce motor activity and a more persistent effect on the peripheral system leading to spinal heat antinociception and delayed fever-like response. The greater neurological response to a second ciguatoxin exposure was associated with elevated concentrations of ciguatoxin in the blood solely over the first hour of exposure. In conclusion, a single exposure to toxin exerts a significant neurological response which may be enhanced with subsequent exposure.
authors.affiliation: Center for Coastal Environmental Health and Biomolecular Research, NOAA-National Ocean Service, Charleston, SC 29412, USA.
authors.forename: Marie-Yasmine
authors.initials: MY
authors.lastname: Bottein Dechraoui
authors.forename: Amir H
authors.initials: AH
authors.lastname: Rezvani
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gordon
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
authors.forename: John S
authors.initials: JS
authors.lastname: Ramsdell
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002922:Ciguatoxins / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D010147:Pain Measurement / Q000379:methods; D011042:Poisons / Q000097:blood*
chemical_list: D011042:Poisons; D002922:Ciguatoxins