Activation of dopamine D2 receptors attenuates neuroinflammation and ameliorates the memory impairment induced by rapid eye movement sleep deprivation in a murine model

Abstract

The proinflammatory state, which may be induced by sleep deprivation, seems to be a determining factor in the development of neurodegenerative processes. Investigations of mechanisms that help to mitigate the inflammatory effects of sleep disorders are important. A new proposal involves the neurotransmitter dopamine, which may modulate the progression of the immune response by activating receptors expressed on immune cells. This study aimed to determine whether dopamine D2 receptor (D2DR) activation attenuates the proinflammatory response derived from rapid eye movement (REM) sleep deprivation in mice. REM sleep deprivation (RSD) was induced in 2-month-old male CD1 mice using the multiple platform model for three consecutive days; during this period, the D2DR receptor agonist quinpirole (QUIN) was administered (2 mg/kg/day i.p.). Proinflammatory cytokine levels were assessed in serum and homogenates of the brain cortex, hippocampus, and striatum using ELISAs. Long-term memory deficits were identified using the Morris water maze (MWM) and novel object recognition (NOR) tests. Animals were trained until learning criteria were achieved; then, they were subjected to RSD and treated with QUIN for 3 days. Memory evocation was determined afterward. Moreover, we found RSD induced anhedonia, as measured by the sucrose consumption test, which is commonly related to the dopaminergic system. Our data revealed increased levels of proinflammatory cytokines (TNFα and IL-1β) in both the hippocampus and serum from RSD mice. However, QUIN attenuated the increased levels of these cytokines. Furthermore, RSD caused a long-term memory evocation deficit in both the MWM and NOR tests. In contrast, QUIN coadministration during the RSD period significantly improved the performance of the animals. On the other hand, QUIN prevented the anhedonic condition induced by RSD. Based on our results, D2DR receptor activation protects against memory impairment induced by disturbed REM sleep by inhibiting neuroinflammation.

Impact of 24 h shifts on urinary catecholamine in emergency physicians: a cross-over randomized trial

“…Epinephrine appeared to be the most relevant fatigue-related catecholamine, which is consistent with literature 28 . Despite low levels of dopamine during a 24 hS, we confirmed previous findings demonstrating that dopamine increased after sleep deprivation 29 and responses may reflect its role as a precursor within the catecholamine pathway. The catecholamine response to shifts was mostly increased in males, as previously shown 30 .…”

Gastrodin Improves Cognitive Dysfunction in REM Sleep-Deprived Rats by Regulating TLR4/NF-κB and Wnt/β-Catenin Signaling Pathways

“…The available evidence suggests that REM sleep deprivation causes learning and memory impairment due to neuroinflammation [25,26], and the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway is involved in sleep-deprivation-induced neuroinflammation [11]. A variety of active ingredients in traditional Chinese medicine, such as Suan-Zao-Ren decoction [27] and curcumin [28], can reduce hippocampal inflammation by inhibiting the TLR4/NF-κB signaling pathway and then improving learning and memory impairment in sleep-deprived rats.…”