Mu and kappa opioid receptors of the periaqueductal gray stimulate and inhibit thermogenesis, respectively, during psychological stress in rats

Abstract

The periaqueductal gray matter (PAG) is rich in mu and kappa opioid receptors, and this system is involved in thermoregulation, analgesia, and defensive behaviors. No study approached the involvement of the PAG opioids in body temperature (Tb) regulation during psychological stress such as restraint. Because activation of mu and kappa receptors increases and reduces Tb, respectively, we tested the hypothesis that they exert excitatory and inhibitory modulation, respectively, of the restraint-induced fever in rats. To this end, Tb, heat loss index (HLI, inference for peripheral vasoconstriction/vasodilation), and oxygen consumption (inference for thermogenesis) were monitored in unanesthetized rats, restrained or unrestrained, before and after intra-PAG microinjection of the selective mu opioid receptor antagonist (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH cyclic, CTAP; 1 and 10 μg/100 nL) or the selective kappa opioid receptor antagonist (nor-binaltorphimine dihydrochloride, nor-BNI; 1 and 4 μg/100 nL) or saline (100 nL). CTAP and nor-BNI did not change the Tb or HLI of euthermic animals. During restraint, Tb increased (1.0 ± 0.1 °C) in all groups; however, this effect was lower in those animals treated with CTAP and higher in animals treated with nor-BNI. The HLI decreased during restraint and increased after animals were released, but this response was not affected by any treatment. Restraint stress increased oxygen consumption (35.9 ± 3.9% elevation), but this response was diminished by CTAP and overstimulated by nor-BNI. Confirming our hypothesis, 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 by affecting the thermogenic but not the heat conservation effector.

The effects of trauma on brain and body: A unifying role for the midbrain periaqueductal gray

“…These perturbations in conscious processing are thought to reflect the dysfunction of endogenous kappa‐opioid receptor binding (Addy, Garcia‐Romeu, Metzger, & Wade, ; Stiefel et al, ). Kappa‐opioid receptors are implicated predominantly in the expression of hyporeactivity, hypotension, bradycardia, and reduced body temperature following stimulation (chemical or electrical) of the ventrolateral periaqueductal gray in the rodent brain (Cristina‐Silva, Martins, Gargaglioni, & Bícego, ; Keay et al, ; Twardowschy & Cysne Coimbra, ). In humans, kappa‐opioid receptor agonists promote alterations in consciousness that may manifest as changes in sensory processing and perceptual integration, visual distortions, kinaesthetic hallucinations, and varied emotional responsiveness (Addy et al, ; Stiefel et al, ).…”

Exercise derived myokine irisin as mediator of cardiorespiratory, metabolic and thermal adjustments during central and peripheral chemoreflex activation

“…In order to infer about the peripheral vasodilation or vasoconstriction of the animals that received the treatment with irisin or vehicle during exposure to hypoxia, we evaluated the heat loss vs conservation through the skin of the tail (T S ). This protocol was performed according to Cristina-Silva et al 38 . One week prior to the experimental day, the rats were anesthetized with i.p.…”

Buprenorphine: prospective novel therapy for depression and PTSD

“…Additionally, a short-acting KOR antagonist was demonstrated to attenuate stress-induced anhedonia (Williams et al, 2018). Moreover, KOR was demonstrated to be involved in body temperature regulation and oxygen consumption during stress (Cristina-Silva, Martins, Gargaglioni, & Bicego, 2017). Thus, it was hypothesized that the effects of buprenorphine on reducing PTSD symptoms are due to its activity at KOR (Lake et al, 2019).…”