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. 2015 Apr 22;40(9):2175–2184. doi: 10.1038/npp.2015.61

Figure 4.

Figure 4

Methamphetamine (MA)-induced hypothermia differs by Taar1 genotype. (a) MALDR mice exhibited hypothermia in response to 1, 2, and 4 mg/kg MA, whereas MAHDR mice exhibited hyperthermia in response to all MA doses. There was a significant line × time × dose interaction (F(25,800)=3.2; p<0.0001) and subsequent analysis identified a significant line × time interaction at each dose of MA (F’s(5,105–165)=7.5–22.8; all p’s<0.0001). Significant changes in temperature across time were found in both lines of mice at all MA doses, except in MALDR mice at 16 mg/kg MA. Thermal data in saline-treated mice were similar for the MALDR and MAHDR lines, and there were no significant differences in body temperature from baseline, except for a small reduction at 180 min. N=12/MADR line and dose; 62–99 days old; replicate 2, selection generation 5. (b, c) Taar1 +/+, and Taar1 +/− mice exhibit hypothermia in response to 2 mg/kg MA, similar to MALDR mice, whereas the hypothermic response is absent in MAHDR and Taar1 −/− mice. Data for 2 mg/kg MA in MADR mice are shown in (b) to facilitate comparison with Taar1 transgenic mice, and are the same data shown in (a). For the Taar1 transgenic mice (c), there was a significant interaction of genotype × time (F(10,80)=3.3 p<0.005) and significant changes in temperature across time were found for all transgenic genotypes, except Taar1 −/−. N=11–13/transgenic line and dose (92–290 days old). (d, e) Ethanol-induced hypothermia was induced by both 2 and 4 g/kg ethanol in MADR mice and Taar1 transgenic mice and no significant differences were found. (d) For MAHDR and MALDR mice, there was a significant time × dose interaction (F(7,329)=17.1; p<0.0001), with greater hypothermia induced by the higher ethanol dose. N=12–13/MADR line; 86–96 days old; replicate 2, selection generation 5. (e) For Taar1 transgenic mice, there was a significant time × dose interaction (F(7,581)=18.0; p<0.0001), with greater hypothermia induced by the higher ethanol dose. N=12–16/ transgenic line and dose (140–220 days old). Mean comparisons collapsed on genotype identified significant differences in core temperature between the baseline measure and after ethanol treatment. Note: Taar1 mice were in short supply and before testing for ethanol-induced hypothermia, had been included in another study in which MA was given 5 times at a frequency of every 48 h, and then allowed a 2-week rest interval between the studies. Shown are means±SEM. +p<0.05 for the difference between the lines or genotypes; *p<0.05 for the difference between baseline temperature and temperature at a given time point within a given genotype, or in the case of ethanol, for the genotypes collapsed. MADR: MA drinking; MALDR: MA low drinking; MAHDR: MA high drinking.