Brain hyperthermia is induced by methamphetamine and exacerbated by social interaction.
Hyperthermia is a symptom of methamphetamine (METH) intoxication and a factor implicated in neurotoxicity during chronic METH use. To characterize the thermic response to METH, it was injected once daily into rats at increasing doses (0, 1, 3, and 9 mg/kg, s.c.) while brain [nucleus accumbens (NAcc), hippocampus] and body (deep temporal muscle) temperatures were continuously monitored. METH produced dose-dependent hyperthermia, with brain structures (especially the NAcc) showing a more rapid and pronounced temperature increase than the muscle. At the highest dose, brain and body temperatures increased 3.5-4.0 degrees C above basal levels and remained elevated for 3-5 hr. Stressful and other high-activity situations such as interaction with a conspecific female are also known to induce a significant hyperthermic response in the rat. A combination of social interaction and METH administration was tested for additive effects. Male rats were exposed daily to a conspecific female for a total of 120 min, and METH was injected at the same doses 30 min after the initial contact with the female. An initial hyperthermic response ( approximately 1.5 degrees C) to social interaction was followed by a large and prolonged hyperthermic response (3.5-5.0 degrees C, 5-7 hr at 9 mg/kg) to METH, which was again stronger in brain structures (especially in the NAcc) than in the muscle. Although the combined effect of the hyperthermic events was not additive, METH administration during social interaction produced stronger and longer-lasting increases in brain and body temperature than that induced by drug alone, heating the brain in some animals near its biological limit (>41 degrees C).
Brown
P Leon
PL
Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA.
Wise
Roy A
RA
Kiyatkin
Eugene A
EA
D019969:Amphetamine-Related Disorders / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D000697:Central Nervous System Stimulants; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007398:Interpersonal Relations; D008297:Male; D008694:Methamphetamine; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans
D000697:Central Nervous System Stimulants; D008694:Methamphetamine