The effects of the β1 antagonist, metoprolol, on methamphetamine-induced changes in core temperature in the rat

Methamphetamine (METH) results in hyperthermia or hypothermia depending on environmental conditions. Here we studied the role of the β1 adrenergic receptor in mediating METH's temperature effects. Core temperature measurements were made telemetrically over a 7.5 h session, two days/week, in test chambers regulated at either 18 °C, 24 °C, or 30 °C ambient temperature. Rats were treated with the β1 antagonist metoprolol (5.0, 10.0, and 15.0 mg/kg) alone (Experiment 1), or in combination with 5.0 mg/kg METH (Experiment 2). In experiment 3, we combined a lower dose range of metoprolol (0.75, 1.5, and 3.0 mg/kg) with 5.0 mg/kg METH at 18 °C and 30 °C. Confirming prior findings, METH alone resulted in hyperthermia in warm (30°) and hypothermia in cool environments (18 °C). Metoprolol alone induced small but significant increases in core temperature. In combination, however, metoprolol reduced METH-induced changes in core temperature. Specifically, at 30 °C, 3.0, 5.0, 10.0, and 15.0 mg/kg metoprolol decreased METH-induced hyperthermia; at 18 °C, all six doses of metoprolol enhanced METH-induced hypothermia. Our metoprolol findings suggest that one component of METH's temperature effects involves increasing core temperature at all ambient conditions via β1 receptors. Since β receptors are involved in brown adipose tissue (BAT)-mediated thermogenesis, skeletal muscle-mediated thermogenesis, heart rate, and the metabolism of glucose and lipids, we discuss each of these as possible mechanisms for metoprolol's effects on METH-induced changes in core temperature.