The effects of methamphetamine on core body temperature in the rat--part 2: an escalating regimen.

RATIONALE: Methamphetamine (METH) induces hyperthermia, which is diminished with chronic treatment in a dose-dependent manner. Our objective was to determine whether the temperature responses produced by a chronic, escalating-dose METH regimen and a chronic, 5.0 mg/kg dose regimen.
METHODS: Rats received pretreatment injections of saline, 5.0 mg/kg METH, 10.0 mg/kg METH (second comparison group), or an escalating-METH regimen (2-9 mg/kg) for 12 days. On day 13, all four groups were challenged with 10.0 mg/kg METH. Temperature measurements were made telemetrically at 24 degrees C ambient temperature.
RESULTS: Escalating pretreatment produced hyperthermia; with successive exposures, the hyperthermic peak shifted to the right. The 5.0-mg/kg-pretreatment group initially showed no change in temperature at 60 min post-treatment but developed hypothermia at 60 min with chronic treatment; at 3 h post-treatment, significant hyperthermia was present and did not diminish with chronic treatment. After the 10.0-mg/kg-METH challenge, the saline-pretreatment group was hyperthermic, and the 10.0-mg/kg-pretreatment group was hypothermic; the 5.0 mg/kg and escalating pretreatment groups were intermediate and were not different from each other. At 3 h post-challenge, no group differences were apparent. Dopamine (DA) and serotonin (5-HT) were not depleted when measured 2 weeks after treatment ended.
CONCLUSIONS: (1) Escalating and 5.0-mg/kg regimens produced different temperature profiles during the 12-day pretreatment period but a similar diminished response to the 10.0-mg/kg-METH challenge on day 13. (2) The diminished temperature responses with chronic treatment occurred in the absence of long-term DA and 5-HT depletions.