Participação dos receptores opióides mu e kappa da substância cinzenta periaquedutal na febre induzida por estresse de contenção

Abstract

The endogenous opioids are involved in analgesia, thermoregulation and physiological responses to various stressful stimuli such as infection, psychological stress and hypoxia. The mu and kappa receptors in the hypothalamus play a role in endotoxin-induced fever and hypoxia-induced anapyrexia (opposite response to fever), respectively. In addition, periaqueductal gray (PAG), which express both mu and kappa receptors, is involved in defence and thermoregulatory responses. Thus, our hypothesis is that mu and kappa opioid receptors in the PAG modulate the restraint-induced fever in rats by activating and inhibiting this response, respectively. To this end, body temperature (Tb) and heat loss index (HLI; inference for heat conservation/loss) and oxygen consumption (VO ; inference for thermogenesis) of unanesthetized Wistar rats submitted or not to restraint stress, was monitored before and after intra-PAG microinjection of the selective mu opioid receptor antagonist (CTAP; 1 and 10 μg/ 100 nL/ animal), the selective kappa-opioid receptor antagonist (nor-BNI; 1 and 4 μg/ 100 nL/ animal), or vehicle (saline; 100nL/ animal). CTAP and nor-BNI did not change the Tb or the HLI of the animals in euthermia. During the restraint stress, Tb increased in all groups of animals. However, this effect was significantly lower in animals treated with CTAP, and significantly higher in animals treated with nor-BNI. No treatment affected HLI, but CTAP decreased thermogenesis and nor-BNI increased thermogenesis. The results indicate that the mu and kappa opioid receptors in the PAG of rats play a pyrogenic and antipyretic role, respectively, during fever induced by restraint stress and these receptors in PAG may not be essential for the maintenance of Tb during euthermia.