Abstract
Hypothalamic orexin neurons are involved in various physiological functions, including thermoregulation. The orexinergic system has been considered as a potent mediator of the exercise response. The present study describes how the antagonization of the orexinergic system by a dual orexin receptor antagonist (DORA) modifies the thermoregulatory process during exercise. Core Body Temperature (CBT) and Spontaneous Locomotor Activity (SLA) of 12 male Wistar rats were recorded after either oral administration of DORA (30 mg/kg or 60 mg/kg) or placebo solution, both at rest and in exercise conditions with treadmill running. DORA ingestion decreased SLA for 8 hours (p < 0.001) and CBT for 4 hours (p < 0.01). CBT (°C) response was independent of SLA. The CBT level decreased from the beginning to the end of exercise when orexin receptors were antagonized, with a dose-dependent response (39.09 ± 0.36 and 38.88 ± 0.28 for 30 and 60 mg/kg; p < 0.001) compared to placebo (39.29 ± 0.31; p < 0.001). CBT increased during exercise was also blunted after DORA administration, but without dose effects of DORA. In conclusion, our results favor the role of orexin in the thermoregulation under stress related to exercise conditions.
Highlights
Hypothalamic orexin neurons are involved in various physiological functions, including thermoregulation
The aim of this study is to evaluate the effect of dual orexin receptor antagonist (DORA) on Core Body Temperature (CBT)
Post hoc analysis reported reduced Spontaneous Locomotor Activity (SLA) during the first 4-hour period after forced feeding for the 30 mg/kg (p < 0.001) and the 60 mg/kg (p = 0.02) DORA 12 dose when compared to the control condition
Summary
Hypothalamic orexin neurons are involved in various physiological functions, including thermoregulation. The present study describes how the antagonization of the orexinergic system by a dual orexin receptor antagonist (DORA) modifies the thermoregulatory process during exercise. Orexin neurons receive inputs from the ventrolateral preoptic area, the locus coeruleus, the dorsal raphe, and the suprachiasmatic and tuberomammillary nuclei (see review in[8]) Their distribution infer a role of orexin in stress induced thermogenesis through glutamatergic excitatory neurotransmission from the dorsomedial hypothalamus to sympathetic premotor neurons in the rostral medullary raphe region[9], resulting in BAT thermogenesis[10]. The stress-related thermal response during exercise may be modulated by different factors including the orexin system Inactivation of both receptor subtypes (using pharmacological antagonization, surgery or in genetically modified animals) previously showed a decrease in CBT and spontaneous motor activity. Measurements of CBT and SLA at rest and during exercise in rats under controlled conditions and after antagonizing the orexinergic system were used to assess this hypothesis
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