The effects of methamphetamine on core body temperature in the rat--part 1: chronic treatment and ambient temperature.

Rationale: Stimulants such as methamphetamine (METH) alter core temperature in a manner that is dependent on ambient temperature and that shows tolerance after chronic use. Our objectives were to (1) determine whether tolerance to METH-induced hyperthermia was a consequence of neurotoxicity to dopamine or serotonin and (2) determine the relationship between ambient temperature and chronic treatment on the METH-induced temperature response.

Materials And Methods: Rats were treated with 1.0, 5.0, or 10.0 mg/kg METH at 24 degrees C (experiment 1) or treated with 5.0 mg/kg METH at 20 degrees C, 24 degrees C, or 28 degrees C (experiment 2). Treatment occurred for 12 days, and temperature measurements were made once per minute telemetrically during 7-h sessions in computer-regulated environments.

Results: Peak increases in core temperature occurred at 60 min post-treatment for the 1.0 and 10.0 mg/kg doses, and at 180 min for the 5.0 mg/kg dose. Tolerance-like effects were seen with chronic 5.0 (mixed results) and 10.0 mg/kg METH in the absence of dopamine or serotonin depletions measured 2 weeks after the completion of treatment. After 5.0 mg/kg METH, variations in ambient temperature resulted in an early flexible change in core temperature (phase 1) (hyperthermia at 28 degrees and hypothermia at 20 degrees ) and a later inflexible hyperthermia (phase 2).

Conclusions: The results suggest that (1) the peak effect of different doses of METH occurs at different times (24 degrees ), (2) the diminished temperature response with chronic METH treatment was not associated with long-term dopamine and serotonin depletions, and (3) a two-phase temperature response to METH may reflect two independent mechanisms.