Time course of brain temperature and caudate/putamen microdialysate levels of amphetamine and dopamine in rats after multiple doses of d-amphetamine.
Brain temperature monitoring and microdialysis were performed simultaneously in the caudate/putamen (CPu) of conscious, freely moving rats dosed with d-amphetamine (AMPH). The brain temperature was determined via a thermistor inserted through a microdialysis guide cannula located in the left CPu, while the microdialysis probe was positioned in the right CPu. The peak AMPH and dopamine (DA) levels were reached 40 to 60 min after dosing, while peak brain temperature was not achieved until 20 to 40 min thereafter in rats becoming moderately hyperthermic. Those rats becoming severely hyperthermic (temperatures above 41.0 degrees C) had microdialysate concentrations of AMPH and DA almost 2-fold higher than those with moderate hyperthermia after the second dose of 5 mg/kg AMPH. However, these peaks were not reached until 60 to 80 min after dosing. This was probably due, in part, to the longer half-life of AMPH in the severely hyperthermic group. The changes in brain temperature observed after exposure to neurotoxic doses of AMPH closely paralleled core body temperature changes previously reported during AMPH exposure. Temperature plays an important role in many types of neurotoxicity, and monitoring brain temperature during microdialysis studies can be done continuously, and with less chance of damage to the microdialysis equipment than most of the traditional methods used to measure core body temperature.
Clausing
P
P
Department of General Toxicology, Scantox, Lille Skensved, Denmark.
Bowyer
J F
JF
D000661:Amphetamine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015259:Dopamine Agents; D000661:Amphetamine; D004298:Dopamine