The Influence of Environmental Temperatures on Neurotoxicity Induced by Methamphetamine in Male Rats

Abstract: Methamphetamine (MAMPH) increases core body temperature at room temperature and decreases it in the cold room. MAMPH at doses ≥ 5.0 mg/kg also induces neural toxicity at room temperature, but not in the cold room. We hypothesized that the neural toxicity of the MAMPH is heat related. Thus, the objectives of these experiments were to investigate the dynamics of heat dissipation and conservation at various ambient temperatures. Forty male Sprague-Dawley rats were divided into four equal groups. Groups 1, 2 and 3 were injected intraperitoneally (i.p.) with saline and one hour later with an equivolume of MAMPH in doses of 2.5, 5.0, or 7.5 mg/kg bwt. Group four was injected with saline/saline. Core body (Tc) and tail skin (Ts) temperatures were recorded with thermistors (YSI series 700) at room temperature (21 ± 1°C) or in a cold room (7 ± 0.5°C) every five minutes for four hours. Tc was used as an index for total body heat, and Ts was used as an index for blood flow to the tail (a measure of heat dissipation /conservation) at various times during the experiment. Analysis of the data (ANOVA and post-hoc) showed that MAMPH at doses of 5.0 and 7.5 mg/kg bwt increased the Tc at room temperature, and decreased the Tc at doses of 2.5, 5.0 and 7.5 mg/kg bwt in the cold room in a dose dependent manner. Analysis of the tail effector mechanism for heat dissipation at room temperature, and for heat conservation in the cold room, demonstrated that Ts does not follow Tc at room temperature, but follows Tc in the cold room. In the cold room, MAMPH treated animals decreased Ts, or probably vasoconstricted the tail as the Tc falls. In contrast, at room temperature, although MAMPH raised the Tc of the animals, there was no evidence for a change in Ts, or no tail vasodilatation. Based on these data, we suggest that MAMPH (i.p.) impair heat dissipation, but not heat conservation. Hence, the accumulated heat in neural tissue may account, in part, for the reported neural toxicity of MAMPH