title: Acute and delayed thermoregulatory response of mice exposed to brevetoxin.
abstract: Thermal dysthesia, characterized by a painful sensation of warm and cool surfaces, is one of many ailments in humans exposed to various marine algal toxins such as brevetoxin (PbTx). There is no animal model to study thermal dysthesia and little is known of the mechanism of action. There is also little known on the acute and delayed thermoregulatory effects of PbTx. In this study, we developed a behavioral system to assess the possible development of thermal dysthesia in mice exposed to PbTx. Female mice were implanted with radiotransmitters to monitor core temperature (Tc) and motor activity (MA). In one experiment, mice were dosed with the control vehicle or 180 microg/kg PbTx and placed on a floor temperature gradient to measure the selected foot temperature (SFT) while air temperature was kept constant. PbTx-treated mice underwent a 10 degrees C reduction in SFT concomitant with a 3 degrees C reduction in Tc within 30 min after exposure. In another study, Tc and MA were monitored in mice maintained in their home cages after dosing with 180 microg/kg PbTx. Tc but not MA increased for 2-5 days after exposure. SFT was unaffected by PbTx when tested 1-12 days after exposure. However, PbTx-treated mice underwent an increase in Tc when placed in the temperature gradient for up to 12 days after exposure. This suggests that PbTx augments the stress-induced hyperthermia from being placed in a novel environment. Overall, acute PbTx exposure leads to a regulated reduction in Tc as characterized by a preference for cooler SFTs and a reduced Tc. Thermal dysthesia was not apparent, but the exaggerated hyperthermic response with a normal SFT in the temperature gradient may suggest an altered processing of thermal stimuli in mice treated with PbTx.
authors.affiliation: Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. gordon.christopher@epa.gov
authors.forename: C J
authors.initials: CJ
authors.lastname: Gordon
authors.forename: K L
authors.initials: KL
authors.lastname: Kimm-Brinson
authors.forename: B
authors.initials: B
authors.lastname: Padnos
authors.forename: J S
authors.initials: JS
authors.lastname: Ramsdell
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008387:Marine Toxins / Q000494:pharmacology*; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology*; D035964:Oxocins; D013686:Telemetry; D000095702:Polyether Toxins
chemical_list: D008387:Marine Toxins; D009498:Neurotoxins; D035964:Oxocins; C053342:brevetoxin; D000095702:Polyether Toxins