Relationship between methamphetamine-induced behavioral activation and hyperthermia

Methamphetamine (METH) changes core temperature and induces behavioral activation. Behavioral activation is also known to change core temperature. The purpose of this report was to 1.) evaluate the extent to which the behavioral activation induced by METH showed a temporal relationship to METH-induced hyperthermia; and 2.) describe the temporal pattern of METH-induced hyperthermia over an extended dose range. Rats were treated with saline or METH (0.5–10.0 mg/kg) in computer-controlled chambers with ambient temperature maintained at 24 °C. Continuous telemetric core temperature measurements were made during a 7 h test period. Behavioral observations were made once every 15 min using an 11-point scale ranging from 0 (quiet awake) to 10 (focused licking or biting). The onset of METH-induced behavioral activation occurred at 15–30 min after treatment for all doses and preceded core temperature increases; the onset of METH-induced hyperthermia ranged from 45 min post-treatment to 120 min post-treatment. This behavior-temperature delay was 15–30 min at the lowest (0.5 and 1.0 mg/kg) and the highest (7.0, 8.0, and 10.0 mg/kg) doses tested; the delay was increased between 1.0 and 4.0 mg/kg METH (105 min delay at 4.0 mg/kg) and then decreased again from 4.0 to 10.0 mg/kg. The strongest relationship between core temperature and behavioral activation occurred at 180 min post-treatment. These data suggest that factors other than behavior are primarily responsible for the observed core temperature effects during the initial post-treatment period (60 min peak); possible effects from movement are masked. For the latter post-treatment period (180 min peak) the stronger relationship between temperature and behavior suggests a role for movement in METH-induced hyperthermia.

Research Highlights
► We studied the relationship between methamphetamine-induced movement and hyperthermia.
► The timing of methamphetamine(METH)-induced hyperthermia depends on dose.
► METH-induced movement may contribute to hyperthermia at 180 min post-treatment.
► At 60 min post-METH, other factors appear to determine the hyperthermic response.