- |||||||||| morphine sulphate / Generic mfg., primidone / Generic mfg.
The Role of TRPM3 Ion Channels in Opioid-Induced Pruritus (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12588;
As TRPM3 shows higher level of co-expression with the μ-opioid receptors in the inhibitory neurons responsible for the pruritic pathway compared to the excitatory neurons for the analgesic pathway, the results are consistent with the claim that the activation of TRPM3 can decrease morphine-induced itch without significant side effects. This study outlines the first distinct phenotype found in the novel mouse model TRPM3DEx17 and provides evidence for a potential new therapy to relieve morphine-induced pruritus by targeting TRPM3.
- |||||||||| morphine sulphate / Generic mfg.
Decreased interhemispheric and corticolimbic white matter fractional anisotropy in chronic back pain patients with long-term opioid usage (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12586;
We searched for correlates in the opioid usage group between anisotropy values and three opioid-related measures- opioid misuse, morphine milligram equivalent, and subjective withdrawal symptoms- but did not find significant associations between these parameters.These findings suggest that long-term opioid usage is associated with changes in structural connectivity between brain regions in the dopaminergic mesocorticolimbic circuitry, which are implicated in pain, reward, and drug addiction processes, and in tracts connecting the left and right frontal lobes through the corpus callosum. More generally, these findings align with current evidence showing analogous compromised mesolimbic white matter integrity in brains of substance-abuse patients.
- |||||||||| Selectivity and efficacy of novel C9-substituted 5-phenylmorphans to bind and activate mu opioid receptors (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12584;
All four compounds displayed high affinity for MOR: Compounds 1, 2, 3, and 4 have MOR Ki values of 0.83 nM, 0.39 nM, 0.76 nM, and 4.23 nM, respectively, with >10-fold selectivity vs. KOR and DOR. All four compounds have EC50 values < 25 nM at MOR, indicating greater potency than morphine (123 nM) and similar potency to nalbuphine (17.3 nM).
- |||||||||| morphine sulphate / Generic mfg.
Adjuvant application of a dopamine D3 receptor agonist to an ineffective morphine dose provides analgesia in a model of chronic pain (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12583;
CAPs of the injured sciatic nerves were strongly decreased compared to the non-injury controls, and neither long-term treatment with morphine or PPX alone changed this phenotype. In contrast, long-term application with the PPX/opioid adjuvant at the low dose (1 mg/kg) induced a clear trend towards a recovery of CAP function.Together, these data suggest that adjuvant treatment of a D3 receptor agonist with morphine at a low and ineffective dose can achieve and maintain analgesia in a peripherally induced CNP model over time, and that this effect may be mediated in part by restoration of function in the injured sciatic nerves.We posit that these findings may lead to the development of a novel pain relief therapeutic that reduces negative side effects associated with high dose opioids, thereby reducing the opioid epidemic.
- |||||||||| morphine sulphate / Generic mfg.
Loss of SUR1 subunits in astrocytes decreases hypersensitivity in neuropathic pain and opioid tolerance models in mice (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12582;
Using genetic approaches, we tested whether the activity of SUR1 in neurons or astrocytes confers antinociception or pronociception in mouse models of neuropathic pain (spinal nerve ligation, SNL), inflammatory pain (Complete Freund’s Adjuvant, CFA), or morphine tolerance...Conversely, stimulating SUR1 expressed in neurons could dampen sensory signaling by acting via KATP channels thereby ameliorating neuropathic pain. Future directions will include the investigation of post-translational modifications/trafficking of SUR1 in neurons vs glia and how each are involved in antinociceptive vs pronociceptive neurotransmission.
- |||||||||| morphine sulphate / Generic mfg.
Elucidating the function of mu opioid receptors in distinct populations of spinal neurons (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12581;
Strikingly, deletion of MOPr in En1-positive neurons did not affect morphine-induced antinociception or straub tail, but completely abolished morphine-induced hyperlocomotion and instead produced a morphine-induced immobility phenotype. Collectively, these results begin to elucidate and dissociate the cell type and circuit mechanisms by which MOPr alter pain perception and movement.
- |||||||||| morphine sulphate / Generic mfg.
Investigating the role of phospholipase C in enhancing opioid pain relief during Hsp90 inhibition (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12579;
We have shown that intrathecal delivery of the heat shock protein 90 (Hsp90) inhibitor 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) in mice enhances the anti-nociceptive potency of morphine by 2-4 fold while significantly reducing side effects, suggesting Hsp90 inhibition as a promising opioid dose reduction approach...Our data suggests that PLC is directly activated by 17-AAG treatment to enhance pain relief and may be a critical component of this evolving opioid reduction strategy. We further report our efforts to measure PLC activity directly in 17-AAG treated spinal cords, along with immunohistochemistry studies to identify the location and cell type in which PLC is upregulated.
- |||||||||| morphine sulphate / Generic mfg.
Behavioral and brain consequences of opioid exposure for more than three months in chronic back pain patients (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12578;
For CBP-op, we measured opioid use from daily prescriptions converted into morphine milligram equivalent (MME)...These results indicate that chronic opioid use in chronic back pain patients leads to increased brain activity, especially in the mesolimbic system, and increased functional and emotional disability. Therefore, long term opioid exposure in chronic back pain has both brain and behavioral negative consequences.
- |||||||||| morphine sulphate / Generic mfg.
Novel mechanisms of peripheral opioid tolerance: involvement of keratinocytes and PDGFR-ß singling (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_12577;
Using a pharmacological approach in mice, we found that intraplantar (i.pl.) co-administration of morphine with imatinib (PDGFR-ß inhibitor), or with PDGFRß-Fc (PDGF-B scavenger), prevented POT...Ongoing studies are determining whether POT could affect expression of PDGF-B in keratinocytes, and whether keratinocytes could, in fact be releasing PDGF-B upon opioid peripheral stimulation. PDGFRβ inhibitors are FDA approved and could be repurposed to prevent peripheral tolerance and reduce opioid side-effects and the risk of addiction, overdose and death.
- |||||||||| morphine sulphate / Generic mfg.
A 5-HT2Ainverse agonist attenuates morphine withdrawal syndrome in the rat. (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_11773;
There were large effect sizes for all of these comparisons. Since pimavanserin is highly selective for the 5-HT2A serotonin receptor, the results suggest that activation of this receptor contributes to opiate physical dependence, and that 5-HT2A inverse agonists may powerfully reduce opiate dependence and withdrawal syndrome.
- |||||||||| morphine sulphate / Generic mfg.
Dissecting opioid-sensitivity of ventral tegmental area dopamine subpopulations (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_11772;
We found differences in baseline intrinsic properties of these subpopulations and differences in responsivity to morphine exposure. We have also profiled the calcium activity of these subpopulations throughout morphine conditioned place preferences for these subpopulations.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Artificial light at night drives sex-specific increases in opioid reward-related behavior in mice (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_11757;
Together, these findings highlight a mechanism by which light at inappropriate times of day may increase propensity for opioid abuse. Future experiments will assess the effects of ALAN on opioid withdrawal, as well as use RNA-sequencing to investigate the potential molecular mechanisms underlying this differential phenotype.
- |||||||||| morphine sulphate / Generic mfg.
Ablation of NPFFR2 in Mice Reduces Response to Type 2 Diabetes Model (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_11701;
Grant Support: MOST 110-2326-B-038-002-MY3, CGMH Grant CMRPD1M0121Neuropeptide FF (NPFF) belongs to a RF-NH2 peptide family and is recognized as a morphine modulating peptide...And NPFFR2 knockout ameliorated the metabolic phenotypes like the imbalance of glucose homeostasis and impaired lipid oxidation. Our evidence shows that the ablation of NPFFR2 attenuates the metabolic symptoms in the type 2 diabetes model.
- |||||||||| morphine sulphate / Generic mfg.
Novel antihyperalgesic agents, strategically substituted agmatines, effectively reduce hypersensitivity without abuse liability (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_11377;
Animals that received morphine, our positive control, showed a significant increase in preference for the morphine-paired chamber compared to saline control animals, as shown by one-way ANOVAs and Student's t-tests...These data show that neither agmatine nor any analog display abuse liability in these two rodent models of reward. These data support the continued development of agmatine and SSAs to address chronic pain.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Striatal mu-opioid receptor activation triggers direct-pathway GABAergic plasticity and induces negative affect (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10899;
Importantly, fentanyl withdrawal caused depression-like behaviors and promoted the reinstatement of fentanyl-seeking behaviors. These data suggest that chronic opioid use triggers GABAergic striatopallidal and striatonigral plasticity to induce a hypodopaminergic state, promoting negative emotions and leading to relapse.
- |||||||||| morphine sulphate / Generic mfg.
Opioid mediated adaptations in the basolateral amygdala circuitry. (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10898;
Morphine mice had increased anxiety-like behavior in marble burying task, which was occluded in mu-opioid receptor knockdown mice. Together, these data highlight the importance of the mu-opioid receptor in BLA paracapsular neurons in morphine induced circuit adaptations and anxiety-like behavior.
- |||||||||| morphine sulphate / Generic mfg.
Motivational shifts during protracted opioid withdrawal: a sex- and dopamine subcircuit-specific effect (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10269;
To address the lack of data during protracted withdrawal, we find that morphine dependent male and female mice subjected toa14-day period of forced drug abstinence display increased morphine intake and motivation for morphine compared to previously non-dependent mice (males: Mann-Whitney p=.0029, n=10,14; female: Mann-Whitney p=.0404, n=12,12)...Further, selective chemogenetic inhibition of the lateral VTA-NAc shell subcircuit (2mg/kg CNO) decreases motivation for sucrose reward in drug-naive mice (Wilcox test p=.0313,n=6), an effect lacking in medial VTA-NAc shell subcircuit targeted mice and viral controls (Wilcox test p=.1250, n=6). This data suggests that motivational shifts away from non-drug rewards during protracted withdrawal is associated with latVTA-NAc hypoactivity that is driven by increased GABAergic inhibition of dopamine cells.
- |||||||||| morphine sulphate / Generic mfg.
Mechanoreceptor activation ameliorates symptoms of opiate withdrawal in rats by modulating mesolimbic GABA and dopamine neurons (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10260;
We aimed to determine whether MStim applied via vibration plate at 80 Hz would ameliorate the effects of morphine withdrawal as manifested behaviorally and electrophysiologically in 52 Wistar rats (n=26 with MStim treatment)...The behavioral assay and electrophysiological measurements indicate a significant anxiolytic effect of MStim treatment on opioid withdrawal. Studies are ongoing that will examine the effect of MStim on subsequent dopamine release in the NAc as well as the effect of MStim on ultrasonic vocalizations, analgesia, and locomotor activity.
- |||||||||| morphine sulphate / Generic mfg.
Heroin sex-specifically regulates orbitofrontal circular RNAs (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10257;
MiRNA-associated pathway analysis of common miRNAs has revealed 16 significantly enriched terms including morphine addiction but also cocaine and amphetamine addiction, consistent with a potential role of circRNAs in miRNAs regulation following heroin self-administration. It appears that despite sex-specific regulation of heroin-associated circRNA, there is convergence on the regulation of common miRNAs that can be important for regulating heroin-associated pathways and therefore contribute to the cellular adaptations that arise from chronic heroin administration.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg., methamphetamine / Generic mfg.
The co-presence of mind-altering substances in Mitragynine as a cause of death (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10227;
More males were affected at 80.1%. 160 of 166 decedents were non-Hispanic whites (96.4%), Asian (n=1), Black (n=1), and Hispanic (n=3).
- |||||||||| morphine sulphate / Generic mfg.
Transcriptional factor pCREB mediates NR2B gene expression in the PAG in morphine withdrawal in rats (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10220;
Our results suggest that MW is associated with pCREB and induction of NR2B in PAG neurons, and that CREB mediates increased expression of NR2B in an epigenetic manner. Understanding the complex relationship between pCREB and NR2B will allow us to formulate novel epigenetic and molecular therapies.
- |||||||||| morphine sulphate / Generic mfg.
Neural signatures of risk-taking vs. risk-avoiding behaviors in the prefrontal cortex of morphine-conditioned rats (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10078;
Taken together, our results suggest that a loss of PL inhibition after opioid conditioning is associated with the formation of contextual reward memory. Furthermore, suppression of excitatory responses to threat and impaired inhibitory signaling of neutral vs. threat contexts in PL may underlie increased risk taking following opioid exposure.
- |||||||||| morphine sulphate / Generic mfg.
Immune checkpoint PD-1 in hippocampal neurons regulates neuronal excitability, synaptic plasticity, and memory (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10025;
Notably, PD-1 functions to suppress neuronal excitability, as Pdcd1-deficient mice show hyperexcitability in DRG nociceptive sensory neurons, leading to pain hypersensitivity and impaired morphine analgesia in mice...Conversely, re-expression of Pdcd1 in PD-1 deficient hippocampal neurons suppresses memory and LTP. These findings suggest that anti-PD-1 treatment has therapeutic potential to counteract cognitive decline.
- |||||||||| morphine sulphate / Generic mfg.
Evaluation of the abuse liability of oxycodone in male and female rats using two approaches: intravenous self-administration and conditioned place preference (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_9779;
Rats were allowed to self-administer saline (negative control), morphine (0.6 mg/kg/infusion) or oxycodone (0.01, 0.03, 0.06 and 0.1 mg/kg) by pressing the active lever on an FR3 schedule...Oxycodone (1, 3 and 5 mg/kg; IP) induced even larger bias between the two compartments (P<0.001) in both male and female rats. These data confirm the high abuse potential of oxycodone in male and female rats and both assays can be used to screen the potential abuse liability of novel therapies as part of the NIH HEAL Initiative’s PSPP program towards discovering novel non-addictive analgesics.
- |||||||||| morphine sulphate / Generic mfg., gabapentin / Generic mfg., duloxetine / Generic mfg.
In vivo PK, side effect profile, and efficacy of multiple classes of analgesics in rats (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_9778;
Power analysis was used to determine the group sizes for the various assays. The results of these studies of clinically used analgesic standards demonstrate the validation of the models and endpoints within the PSPP program and highlight the goal of providing a robust platform to accelerate the discovery and preclinical development of non-opioid, non-addictive treatments for pain.
- |||||||||| morphine sulphate / Generic mfg.
Mu opioid receptor expression defines a nociceptive neural ensemble in the ventrolateral periaqueductal gray (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_9737;
With this approach, we discovered that vlPAG MOR+ neurons broadly demonstrate increased calcium activity in response to acutely noxious stimuli that was suppressed by morphine...In total, we have uncovered important properties of MOR+ neuronal populations and pathways in the vlPAG, a critical nociceptive brain region. These data will inform targeted interventions to selectively modulate pain-related neurocircuitry and thereby mitigate the harmful effects of prescription opiates.
- |||||||||| morphine sulphate / Generic mfg.
Opto-mass: a high-throughput engineering platform for genetically encoded fluorescent sensors enabling all optical in vivo detection of monoamines and opioids (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_9204;
μMASS2A was expressed in nucleus accumbens of Penk-cre mice and detected dose-dependent morphine administration in vivo using fiber photometry...Traditional techniques screen sensors one by one, Opto-MASS presents a method to rapidly develop in vivo capable optogenetic sensors by functional screening of thousands of sensor variants expressed in mammalian cells. We showcased our platforms versatility by optimizing monoamine and opioid sensors, highlighting the ability to engineer optogenetic sensors for neurotransmitters with diverse physiological roles.
- |||||||||| morphine sulphate / Generic mfg.
A novel µ-opioid receptor transgenic Cre rat: cellular and behavioral characterization (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8993;
We test basal response to pain, morphine analgesia and tolerance... The novel Oprm1-Cre transgenic rat can be used to study the role of brain Oprm1-expressing cells in opioid addiction- and pain-related behaviors, as well as other opioid-mediated learned and innate behaviors.
- |||||||||| morphine sulphate / Generic mfg.
BDNF expression in the mesolimbic reward system in the extinction of morphine place preference (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8981;
In females, preliminary results showed increased BDNF expression in the HPC, similar to males. Overall, our data shows that although increased BNDF expression in the AMY might be responsible for contextual learning during extinction training, the increased BDNF expression in the HPC plays a key role in the successful extinction of opioids seeking behavior.
- |||||||||| morphine sulphate / Generic mfg.
Deep Brain Stimulation Increases BDNF After Extinction of Morphine CPP (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8969;
Our data suggest a potential role for hippocampal/accumbal connections in DBS-mediated extinction facilitation, which may involve axonal BDNF transport. This work was supported by NIH-MBRS Score-1SC2DA047809-02 and NIH-RISE-R25GM061838.
- |||||||||| morphine sulphate / Generic mfg.
Estradiol Increases Anxiety During Early Morphine Withdrawal (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8968;
Our data revealed that during early morphine withdrawal, female rats given estradiol on first day of the repeating hormone replacement cycle showed greater anxiety when compared with morphine withdrawn female vehicle controls and morphine withdrawn male rats (in light-dark box testing). Current analysis is underway to understand the extent which hormone treatment influences the severity of somatic withdrawal.
- |||||||||| morphine sulphate / Generic mfg., amphetamine / Generic mfg.
Sex difference in acute withdrawal following low doses of psychostimulant-opioid combination (speedball) (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8952;
These sex differences suggest that psychostimulant-opioid combinations may pose greater health risks for females. The present findings demonstrate that the methods we have used to assess drug-induced changes in 24-hour activity patterns, including acute withdrawal, can be validly used with both female and male rats.
- |||||||||| morphine sulphate / Generic mfg.
Modulation of 5-HT release by dynorphin mediates social deficits during opioid withdrawal (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8912;
To model protracted opioid withdrawal, we designed a procedure in which mice are administered escalating doses of morphine in conditioned place preference (CPP) chambers and tested for social behaviors after three weeks of abstinence...Finally, fiber photometry recordings with the genetically encoded GRAB5-HT sensor revealed that during withdrawal, KORs reduce the 5-HT release into the NAc that normally occurs during social interactions. These results define a novel neuromodulatory mechanism that is engaged during protracted opioid withdrawal to induce maladaptive deficits in prosocial behaviors, which in humans afflicted with OUD contribute to relapse.
- |||||||||| morphine sulphate / Generic mfg.
The Effects of Opioids on Stress-Induced Neuroplasticity (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8864;
Mice that underwent chronic stress alone also had increased neural activity in the dentate gyrus and BLA, however, this stress-induced hyperactivity was counteracted by morphine exposure. These data highlight the complexity of stress and opioid interactions and suggest a buffering effect of morphine against neuroplastic effects induced by stress.
- |||||||||| morphine sulphate / Generic mfg.
Antinociceptive actions of mitochondrial uncoupling drugs in rat and mouse (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8540;
Hindpaw injection of BAM15 (0.2µg/µl) 1 hour prior to a low systemic dose (0.03mg/kg) morphine prevented hyperalgesia observed 30 minutes after morphine...This effect was observed in a subset of capsaicin-sensitive and IB4-binding neurons, but not in neurons negative for both indicators (n=8-13 cells each). Experiments are underway to identify the molecular mechanisms responsible for activation of K_ATP channels by DNP and BAM15 and to determine whether additional mechanisms contribute to anti-hyperalgesic effects in vivo.
- |||||||||| morphine sulphate / Generic mfg.
Biomarkers of the opioid-induced neuronal degeneration in mouse brain and plasma (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8445;
To investigate the effect of chronic opioid use we treated mice with either water or morphine (15 mg/kg) for 30-60 days...The findings of this project support the hypothesis that chronic opioid use causes a negative impact on neuronal health. Our data also suggest that measuring the level of neuronal and pro-inflammatory biomarkers in blood samples may serve as a diagnostic tool to monitor drug-induced neuronal degeneration in research and clinical settings.
- |||||||||| morphine sulphate / Generic mfg.
Hiv-1 tat and opiate use induce synaptic instability in dorsal striatum (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8046;
These results suggest that the dysregulation of AMPAr trafficking may be driven by an increase in Ca2+ via the NMDAr subunits, leading to the disruption of the AMPAr GluA1/2 subunit expression pattern in the dorsal striatum. Therefore, the increased sensitivity for morphine on the CPP task may be attributed to the dysregulation of AMPAr subunit composition observed in the dorsal striatum of HIV-1 Tat+ ovx transgenic mice.
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