We have recently reported that the serotonin (5-HT) projections from the midbrain's raphe nuclei that contains 5-HT cell bodies may play a role both in heat production and in heat loss. The purpose of the present study was to clarify the involvement of 5-HT in the ventral tegmental area (VTA), where 5-HT is suggested to participate in thermoregulation, using the combined methods of telemetry, microdialysis, and high performance liquid chromatography, with a special emphasis on regulation of the body temperature (T-b) in freely moving rats. First, we measured changes in Tb, tail skin temperature (T-tail; an index of heat loss), heart rate (HR; an index of heat production), locomotor activity (Act), and levels of extra cellular monoamines in the VTA during cold (5 degrees C) or heat (35 degrees C) exposure. Subsequently, we perfused citalopram (5-HT re-uptake inhibitor) into the VTA and measured the thermoregulatory parameters and monoamines release. Although T-b, T-tail, and HR changed during both exposures, significant changes in extracellular level of 5-HT (138.7 +/- 12.7% baseline, p < 0.01), but not dopamine (DA) or noradrenaline (NA) were noted in the VTA only during heat exposure. In addition, perfusion of citalopram into the VTA increased extracellular 5-FIT levels (221.0 +/- 52.2% baseline, p < 0.01), but not DA or NA, while Tb decreased from 37.4 +/- 0.1 degrees C to 36.8 +/- 0.2 degrees C (p<0.001),Ttail increased from 26.3 +/- 0.4 degrees C to 28.4 +/- 0.4 degrees C (p < 0.001), and HR and Act remained unchanged. Our results suggest that the VTA is a key area for thermoregulation, and 5-HT, but not DA or NA, modulates the heat loss system through action in the VTA. (C) 2017 Elsevier B.V. All rights reserved.