scholarly journals Anhedonia to music and mu-opioids: Evidence from the administration of naltrexone

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Adiel Mallik ◽  
Mona Lisa Chanda ◽  
Daniel J. Levitin
Keyword(s):  
Mu Opioids

Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib in Humans

2006 ◽  
Vol 105 (5) ◽  
pp. 1016-1023 ◽  
Author(s):  
Andreas Tröster ◽  
Ruth Sittl ◽  
Boris Singler ◽  
Martin Schmelz ◽  
Jürgen Schüttler ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Rating Scale ◽  
Control Level ◽  
Numeric Rating Scale ◽  
Cyclooxygenase 2 ◽  
Controlled Study ◽  
Double Blind ◽  
Antinociceptive Effects ◽  
Current Densities ◽  
Mu Opioids

Background Numerous experimental and clinical studies suggest that brief opioid exposure can enhance pain sensitivity. It is suggested that spinal cyclooxygenase activity may contribute to the development and expression of opioid tolerance. The aim of the investigation was to determine analgesic and antihyperalgesic properties of the cyclooxygenase-2 inhibitor parecoxib on remifentanil-induced hypersensitivity in humans. Methods Fifteen healthy male volunteers were enrolled in this randomized, double-blind, placebo-controlled study in a crossover design. Transcutaneous electrical stimulation at high current densities was used to induce spontaneous acute pain (numeric rating scale 6 of 10) and stable areas of pinprick hyperalgesia. Pain intensities and areas of hyperalgesia were assessed before, during, and after a 30-min intravenous infusion of remifentanil (0.1 microg x kg x min) or placebo (saline). Parecoxib (40 mg) was administered intravenously either with onset of electrical stimulation (preventive) or in parallel to the remifentanil infusion. Results Remifentanil reduced pain and mechanical hyperalgesia during the infusion, but upon withdrawal, pain and hyperalgesia increased significantly above control level. Preventive administration of parecoxib led to an amplification of remifentanil-induced antinociceptive effects during the infusion (71.3 +/- 7 vs. 46.4 +/- 17% of control) and significantly diminished the hyperalgesic response after withdrawal. In contrast, parallel administration of parecoxib did not show any modulatory effects on remifentanil-induced hyperalgesia. Conclusion The results confirm clinically relevant interaction of mu opioids and prostaglandins in humans. Adequate timing seems to be of particular importance for the antihyperalgesic effect of cyclooxygenase-2 inhibitors.

scholarly journals Mu-opioids suppress GABAergic synaptic transmission onto orbitofrontal cortex pyramidal neurons with subregional selectivity

2020 ◽  
Author(s):  
Benjamin K. Lau ◽  
Brittany P. Ambrose ◽  
Catherine S. Thomas ◽  
Min Qiao ◽  
Stephanie L. Borgland
Keyword(s):  
Synaptic Transmission ◽  
Opioid Receptor ◽  
Orbitofrontal Cortex ◽  
Pyramidal Neurons ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Inhibitory Synaptic Transmission ◽  
Receptor Coupling ◽  
Mu Opioids ◽  
Gabaergic Synaptic Transmission

AbstractThe orbitofrontal cortex (OFC) plays a critical role in evaluating outcomes in a changing environment. Administering opioids to the OFC can alter the hedonic reaction to food rewards and increase their consumption in a subregion specific manner. However, it is unknown how mu-opioid signalling influences synaptic transmission in the OFC. Thus, we investigated the cellular actions of mu-opioids within distinct subregions of the OFC. Using in-vitro patch clamp electrophysiology in brain slices containing the OFC, we found that the mu-opioid agonist, DAMGO produced a concentration-dependant inhibition of GABAergic synaptic transmission onto medial OFC (mOFC), but not lateral OFC (lOFC) neurons. This effect was mediated by presynaptic mu-opioid receptor activation of local parvalbumin (PV+)-expressing interneurons. The DAMGO-induced suppression of inhibition was long-lasting and not reversed upon washout of DAMGO, or by application of the mu-opioid receptor antagonist, CTAP, suggesting an inhibitory long-term depression (iLTD) induced by an exogenous mu-opioid. We show that LTD at inhibitory synapses is dependent on downstream cAMP/PKA signaling, which differs between the mOFC and lOFC. Finally, we demonstrate that endogenous opioid release triggered via moderate physiological stimulation can induce LTD. Taken together, these results suggest that presynaptic mu-opioid stimulation of local PV+ interneurons induces a long-lasting suppression of GABAergic synaptic transmission, which depends on subregional differences in mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascade. These findings provide mechanistic insight into the opposing functional effects produced by mu-opioids within the OFC.Significance StatementConsidering that both the OFC and the opioid system regulate reward, motivation, and food intake; understanding the role of opioid signaling within the OFC is fundamental for a mechanistic understanding of the sequelae for several psychiatric disorders. This study makes several novel observations. First, mu-opioids induce a long-lasting suppression of inhibitory synaptic transmission onto OFC pyramidal neurons in a regionally selective manner. Secondly, mu-opioids recruit PV+ inputs to suppress inhibitory synaptic transmission in the mOFC. Thirdly, the regional selectivity of mu-opioid action of endogenous opioids is due to the efficacy of mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascades. These experiments are the first to reveal a cellular mechanism of opioid action within the OFC.

Opioid-glutamate interactions in rat locus coeruleus neurons

1993 ◽  
Vol 70 (3) ◽  
pp. 931-937 ◽  
Author(s):  
S. Oleskevich ◽  
J. D. Clements ◽  
J. T. Williams
Keyword(s):  
Nmda Receptor ◽  
Locus Coeruleus ◽  
Outward Current ◽  
Experimental Manipulation ◽  
Extracellular Potassium ◽  
Opioid Agonist ◽  
Membrane Hyperpolarization ◽  
Mu Opioid ◽  
Bath Application ◽  
Mu Opioids

1. The effect of mu-opioids on the glutamate response was investigated in rat locus coeruleus (LC) neurons by intracellular recording in the brain slice preparation. Glutamate responses were evoked by bath application of selective glutamate agonists, glutamate iontophoresis, and stimulation of excitatory afferents. 2. The mu-opioid agonist D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO; 1 microM) potentiated the response to bath application of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid by 91 and 142%, respectively, in slices cut in the horizontal plane. The mechanism of action of this effect was investigated under conditions that limited the DAMGO-induced hyperpolarization and improved the space clamp of the neuron through 1) addition of barium, 2) increase in extracellular potassium concentration, 3) sectioning of the LC in the coronal plane, and 4) addition of carbenoxolone. Each experimental manipulation decreased the DAMGO outward current and reduced the mu-opioid potentiation of the glutamate response. The results suggest that the mu-opioid-mediated potentiation of the glutamate response is dependent on membrane hyperpolarization. 3. Neither forskolin nor the phorbol ester 4b-phorbol 12,13-dibutyrate (PDBu) altered the glutamate-mediated inward currents. The potentiation of the glutamate response by DAMGO was not affected by PDBu. 4. The mu-opioids DAMGO and [met]5enkephalin (10 microM) did not significantly affect the NMDA receptor-mediated depolarization (mean 14%) evoked by local application of glutamate but inhibited the NMDA receptor-mediated synaptic potential (mean 25%).(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Blocking mu-opioid receptors inhibits social bonding in rituals

2020 ◽  
Author(s):  
Sarah Jane Charles ◽  
Miguel Farias ◽  
Valerie van Mulukom ◽  
Ambikananda Saraswati ◽  
Simon Dein ◽  
...  
Keyword(s):  
Social Bonding ◽  
Social Scientists ◽  
Double Blind ◽  
Mu Opioid ◽  
Religious Ritual ◽  
Religious Rituals ◽  
Before And After ◽  
Human Practices ◽  
Mu Opioids

Religious rituals are universal human practices, generally practiced in groups. Social scientists have highlighted for over 100 years its role in bonding individuals, but the mechanisms underlying this function have yet to be explored. Here we tested the role of mu-opioids in fostering social bonding in rituals across two double-blind studies. For both studies a mu-opioid blocker (Naltrexone) was taken before the ritual and we assessed strength of social bonding before and after the ritual. Participants were randomly allocated into a placebo or Naltrexone condition. For study 1 (N = 9), we conducted a pilot, yoga-based ritual session in our lab. In study 2 (N = 24), we conducted a naturalistic field study with participants who regularly attended an Afro-Brazilian religious ritual. We found the same effect across both studies, where Naltrexone lead to significantly lower social bonding compared to placebo. These studies show that mu-opioids play a significant role in experiences of social bonding within ritual contexts.

scholarly journals Blocking mu-opioid receptors inhibits social bonding in rituals

2020 ◽  
Vol 16 (10) ◽  
pp. 20200485 ◽  
Author(s):  
S. J. Charles ◽  
M. Farias ◽  
V. van Mulukom ◽  
A. Saraswati ◽  
S. Dein ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Social Bonding ◽  
Mu Opioid Receptors ◽  
Double Blind ◽  
Mu Opioid ◽  
Religious Traditions ◽  
Religious Rituals ◽  
Human Practices ◽  
Mu Opioids

Religious rituals are universal human practices that play a seminal role in community bonding. In two experiments, we tested the role of mu-opioids as the active factor fostering social bonding. We used a mu-opioid blocker (naltrexone) in two double-blind studies of rituals from different religious traditions. We found the same effect across both studies, with naltrexone leading to significantly lower social bonding compared with placebo. These studies suggest that mu-opioids play a significant role in experiences of social bonding within ritual contexts.

scholarly journals Cutaneous Sensory Neurons Expressing the Mrgprd Receptor Sense Extracellular ATP and Are Putative Nociceptors

2008 ◽  
Vol 99 (4) ◽  
pp. 1581-1589 ◽  
Author(s):  
G. Dussor ◽  
M. J. Zylka ◽  
D. J. Anderson ◽  
E. W. McCleskey
Keyword(s):  
Sensory Neurons ◽  
Sensory Modality ◽  
Atp Release ◽  
Extracellular Atp ◽  
Stratum Granulosum ◽  
P2x3 Receptors ◽  
Long Duration ◽  
Mouse Dorsal Root Ganglion ◽  
Mu Opioids ◽  
External Stimuli

Sensory neurons expressing the Mrgprd receptor are known to innervate the outermost living layer of the epidermis, the stratum granulosum. The sensory modality that these neurons signal and the stimulus that they respond to are not established, although immunocytochemical data suggest they could be nonpeptidergic nociceptors. Using patch clamp of dissociated mouse dorsal root ganglion (DRG) neurons, the present study demonstrates that Mrgprd+ neurons have several properties typical of nociceptors: long-duration action potentials, TTX-resistant Na+ current, and Ca2+ currents that are inhibited by mu opioids. Remarkably, Mrgprd+ neurons respond almost exclusively to extracellular ATP with currents similar to homomeric P2X3 receptors. They show little or no sensitivity to other putative nociceptive agonists, including capsaicin, cinnamaldehyde, menthol, pH 6.0, or glutamate. These properties, together with selective innervation of the stratum granulosum, indicate that Mrgprd+ neurons are nociceptors in the outer epidermis and may respond indirectly to external stimuli by detecting ATP release in the skin.

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