Participação do sistema endocanabinoide central na termorregulação durante as atividades físicas espontânea e forçada

Abstract

Introduction: The endocannabinoid system (ECS) plays an important role on regulation of body temperature (Tb) and also modulates several behaviors that interfere on thermoregulation, such as locomotion. In addition, the ECS is activated by demand and it has been shown that both central and peripheral endocannabinoids levels are increased during exercise, an important thermal stressor. However, it remains unclear whether the thermal effects mediated by the ECS are related to their behavioral effects, and if their activation participates in thermoregulatory adjustments during exercise. Aim: The aim of this study was to investigate the role of central anandamide (AEA) on thermoregulatory responses in two distinct experimental models of physical activities: during spontaneous locomotor activity (SLA) and forced physical exercise. Methods: Adult Wistar rats received intracerebroventricular injections of AEA and vehicle, both in resting condition (in the two phases of higher and smaller SLA and, consequently, of Tb), as well as before a progressive treadmill exercise until fatigue. During the spontaneous activity protocol, Tb and SLA were collected continuously and simultaneously; during the forced activity protocol, Tb and skin tail temperature (Tt – used to determine the heat dissipation ability) were recorded. Physical performance and hypothalamic neuronal recruitment after exercise were also evaluated. Finally, to investigate whether recurrent activation of ECS alters the expression of its components in adulthood, weanling Wistar rats (21 days) underwent a physical training protocol or were with fed palatable diet for 8 weeks. After such period, the expression of the CB1 receptor and NAPE-PLD (enzyme responsible for the AEA synthesis) in the brains were quantified. Results: Central AEA treatment in resting condition during the circadian rhythm induced a potent and persistent increase in Tb in the two phases of the cycle, getting even which overlapped the characteristic hyperthermia of the dark phase. This increase in Tb occurred independently of changes on locomotor behavior and food intake. However, this thermal effect of AEA appears to alter the locomotor behavior profile, leading to a reduction of spontaneous activity, possibly as an adaptive mechanism in response to pronounced hyperthermia. On the other hand, during the 9 forced physical exercise, AEA treatment did not alter the thermoregulatory responses, but increased c-Fos expression in hypothalamic nuclei (such as the paraventricular nucleus of the hypothalamus – PVN – and medial preoptic área – mPOA), and improved physical performance. Physical training and palatable diet showed more pronounced effects in brain regions involved in autonomic control of the Tb, where the expression of CB1 receptor and of NAPE-PLD enzyme were reduced mainly in the hypothalamus and the preoptic área. Conclusions: The results of this study show that increased bioavailability of AEA central, through its intracerebroventricular administration, induces a increase in Tb during resting condition, and its thermal response can occur independently of behavioral changes. On the other hand, the thermoregulatory adjustments during forced exercise are not affected by the AEA. However, the animals show improved physical performance and increased hypothalamic neuronal recruitment, which could have contributed to this ergogenic effect, not related to thermoregulation. Finally, induction of recurrent ECS activation alters the expression of its componentes, being the hypothalamus the more responsive area, where both the physical training and palatable diet reduced the expression of CB1 receptor and NAPE-PLD.