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Acute injection of dopamine/noradrenaline reuptake inhibitor affects brain and core temperature in the rat

Wistar male rats were used. A telemetry device (TA10TA-F20) was implanted in the peritoneal cavity. Two intracerebral guides were implanted, one in the left PO/AH for the microdialysis probe, and one in the right frontal cortex for measuring brain temperature (Tbrain). On the day of experiment (48 h after surgery), guides were replaced by a microdialysis probe (MAB 6-14) and a thermocouple probe (HYP-O-SLE). The thermocouple for skin temperature was also attached on the dorsal surface of the skin. After 2 h of baseline collections, rats randomly received either an intraperitoneal injection of 17 mg/kg of BUP (n=6) or physiological saline (1 mL/kg) (n=6). Microdialysis samples were collected every 20 min for 180 min. Tbrain, Tcore and tail skin temperature (Ttail), an index of heat loss response, were measured every 5 minutes. NA, DA and 5-HT in the PO/AH were analysed by an off-line HPLC (Sarre et al. 1997). The average concentration for 1 h before drug administration was considered as the baseline release and was defined as 100 %. Differences between data were evaluated for statistical significance by using repeated measured analysis of variance (ANOVA) followed by Bonferroni/Dunn’s post hoc tests. Values are expressed as the mean ± SEM. The significance level was set at p<0.05. Results Both NA and DA levels in the PO/AH significantly increased after BUP injection compared with the baseline levels (NA; 408 ± 121%, DA; 331 ± 152%, 40 min after injection, p < 0.01). There was no effect on 5-HT release. These changes were accompanied by a significant decrease in Ttail and increase in both brain and abdominal temperature compared with the baseline levels (Ttail: -1.9 ± 0.8 o C, Tbrain: 0.7 ± 0.1 o C, Tcore: 0.5 ± 0.1 o C, n=6, 40 min after injection, p < 0.05). No effects of saline injection were observed on NA, DA and 5-HT in the PO/AH on the thermoregulatory responses. The tip of the microdialysis probe was correctly positioned into the PO/AH in all these animals. Discussion/Conclusion An acute injection of BUP induced an increase in brain and core temperature either by decreasing heat loss or by increasing heat production responses in freely moving rats. These thermal responses were accompanied by an increase in the extracellular concentrations of NA and DA with no effect of 5-HT in the PO/AH of freely moving rats. These results suggest that an acute injection of BUP acts on the brain. Moreover, these results support the previous findings in humans that acute BUP ingestion increases body temperature during exercise (Hasegawa et al. 2004), indicating a possible important role for these neurotransmitters for thermoregulation.