Signaling mechanisms of μ-opioid receptor (MOR) in the hippocampus: disinhibition versus astrocytic glutamate regulation

Nam, Min‐Ho; Won, Woojin; Han, Kwan Hee; Lee, C. Justin

doi:10.1007/s00018-020-03595-8

Cited by 12 publications

(9 citation statements)

References 107 publications

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“…The opioid system also potently modulates the mesolimbic circuitry, limbic circuitry, cortical and hippocampal circuitry, and various brain regions underlying motivation, fear responses, and cognitive functions (Puryear et al, 2020). MORs are predominantly expressed on GABAergic inhibitory interneurons and exert a potent disinhibitory effect on excitatory neurons (Nam et al, 2021).…”

Section: Role Of Opioids Analgesics In Postoperative Consciousness Im...mentioning

confidence: 99%

Opioid-induced short-term consciousness improvement in patients with disorders of consciousness

Wang²,

Zhuang³

et al. 2023

Front. Neurosci.

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IntroductionEffective treatment to facilitate recovery from prolonged disorders of consciousness is a complex topic for the medical community. In clinical practice, we have found that a subset of patients has a short-term improvement of consciousness after general anesthesia.MethodsTo determine the clinical factors responsible for the consciousness improvement, we enrolled 50 patients with disorders of consciousness who underwent surgery from October 2021 to June 2022. Their states of consciousness were evaluated before surgery, within 48 h after surgery, and 3 months after surgery. Clinical-related factors and intraoperative anesthetic drug doses were collected and compared between patients with and without consciousness improvement. Independent associations between selected factors and postoperative improvement were assessed using multivariate logistical regression analyses.ResultsPostoperative short-term consciousness improvement was found in 44% (22/50) of patients, with significantly increased scores of auditory and visual subscales. Patients with traumatic etiology, a preoperative diagnosis of minimally conscious state, and higher scores in the auditory, visual, and motor subscales were more likely to have postoperative improvement. This short-term increase in consciousness after surgery correlated with patients’ abilities to communicate in the long term. Furthermore, the amount of opioid analgesic used was significantly different between the improved and non-improved groups. Finally, analgesic dose, etiology, and preoperative diagnosis were independently associated with postoperative consciousness improvement.DiscussionIn conclusion, postoperative consciousness improvement is related to the residual consciousness of the patient and can be used to evaluate prognosis. Administration of opioids may be responsible for this short-term improvement in consciousness, providing a potential therapeutic approach for disorders of consciousness.

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Section: Role Of Opioids Analgesics In Postoperative Consciousness Im...mentioning

confidence: 99%

Opioid-induced short-term consciousness improvement in patients with disorders of consciousness

Wang²,

Zhuang³

et al. 2023

Front. Neurosci.

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“…The hippocampus is also part of the MOR-modulated DMN and has stronger functional connectivity with other DMN regions in ASD compared to controls [78]. Moreover, MOR modulates the hippocampal neurogenesis, mediating a negative opioid effect, whereas a positive effect can be seen in MOR null knock-out mice [79, 80]. The animal models of ASD present an impaired hippocampal neurogenesis, possibly explaining some of the behavioral phenotypes of the disorder [81].…”

Section: Discussionmentioning

confidence: 99%

Dopamine D2R and opioid MOR availability in autism spectrum disorder

Noppari,

Tuisku,

Lukkarinen

et al. 2024

Preprint

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Opioid and dopamine receptor systems are implicated in the pathoetiology of autism, but in vivo human brain imaging evidence for their role remains elusive. Here, we investigated regional type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities and regional interactions between the two neuromodulatory systems associated with autism spectrum disorder (ASD). In vivo positron emission tomography (PET) with radioligands [11C]raclopride (D2R) and [11C]carfentanil (MOR) was carried out in 16 adult males with high functioning ASD and 19 age and sex matched controls. Regional group differences in D2R and MOR receptor availabilities were tested with linear mixed models and associations between regional receptor availabilities were examined with correlations. There were no group differences in whole-brain voxel-wise analysis of DR2 but ROI analysis presented a lower overall mean D2R availability in striatum of the ASD versus control group. Post hoc regional analysis revealed reduced D2R availability in nucleus accumbens of the ASD group. The whole-brain voxel-wise analysis of MOR revealed precuneal up-regulation in the ASD group, but there was no overall group difference in the ROI analysis for MOR. MOR down-regulation was observed in the hippocampi of the ASD group in a post hoc analysis. Regional correlations between D2R and MOR availabilities were weaker in the ASD group versus control group in the amygdala and nucleus accumbens. These alterations may translate to disrupted modulation of social motivation and reward in ASD.

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“…Another possible explanation is that MOR activation directly causes postsynaptic excitation (Margolis et al, 2014) or augments postsynaptic responses to NMDA application (Martin et al, 1997). Finally, non-neuronal mechanisms may be involved such as MOR activation causing astrocytes to release glutamate (Nam et al, 2021) to excite respiratory-related neurons and increase burst amplitude. Additional studies are required to determine whether neuron-neuron or neuron-astrocyte communication underlies the MOR-dependent transformation of respiratory motor output.…”

Section: Potential Mechanisms Underlying the Burst Amplitude Increasementioning

confidence: 99%

Mu-opioid receptor-dependent transformation of respiratory motor pattern in neonates in vitro

et al. 2022

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Endogenous opioid peptides activating mu-opioid receptors (MORs) are part of an intricate neuromodulatory system that coordinates and optimizes respiratory motor output to maintain blood-gas homeostasis. MOR activation is typically associated with respiratory depression but also has excitatory effects on breathing and respiratory neurons. We hypothesized that low level MOR activation induces excitatory effects on the respiratory motor pattern. Thus, low concentrations of an MOR agonist drug (DAMGO, 10–200 nM) were bath-applied to neonatal rat brainstem-spinal cord preparations while recording inspiratory-related motor output on cervical spinal roots (C4-C5). Bath-applied DAMGO (50–200 nM) increased inspiratory motor burst amplitude by 40–60% during (and shortly following) drug application with decreased burst frequency and minute activity. Reciprocal changes in inspiratory burst amplitude and frequency were balanced such that 20 min after DAMGO (50–200 nM) application, minute activity was unaltered compared to pre-DAMGO levels. The DAMGO-induced inspiratory burst amplitude increase did not require crossed cervical spinal pathways, was expressed on thoracic ventral spinal roots (T4-T8) and remained unaltered by riluzole pretreatment (blocks persistent sodium currents associated with gasping). Split-bath experiments showed that the inspiratory burst amplitude increase was induced only when DAMGO was bath-applied to the brainstem and not the spinal cord. Thus, MOR activation in neonates induces a respiratory burst amplitude increase via brainstem-specific mechanisms. The burst amplitude increase counteracts the expected MOR-dependent frequency depression and may represent a new mechanism by which MOR activation influences respiratory motor output.

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Signaling mechanisms of μ-opioid receptor (MOR) in the hippocampus: disinhibition versus astrocytic glutamate regulation

Cited by 12 publications

References 107 publications

Opioid-induced short-term consciousness improvement in patients with disorders of consciousness

Opioid-induced short-term consciousness improvement in patients with disorders of consciousness

Dopamine D2R and opioid MOR availability in autism spectrum disorder

Mu-opioid receptor-dependent transformation of respiratory motor pattern in neonates in vitro

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