- |||||||||| fentanyl citrate / Generic mfg.
Estradiol protects against pain-facilitated fentanyl use via suppression of opioid-evoked dopamine activity (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10825;
Instead, we demonstrate the therapeutic potential of E2 treatment in males and its ability to reverse the effects of pain on VTADA function and fentanyl use via VTA estrogen receptors. These findings are the first to implicate a role for gonadal hormones in pain-facilitated opioid use and provide novel therapeutic targets within the mesolimbic DA reward circuitry that may contribute to pain-related motivational impairments and risk for opioid abuse.
- |||||||||| fentanyl citrate / Generic mfg.
Examining how prelimbic cortical neuronal ensembles encode behaviors during fentanyl vapor self-administration (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10824;
Following data collection, we utilized deep behavior learning to perform a fine-grain analysis of behavior, which we overlayed with calcium transient data. We are leveraging these cutting-edge imaging technologies and behavioral analysis tools to gain a deeper insight into how neuronal ensembles in the prefrontal cortex encode opioid-related behaviors during fentanyl vapor self-administration and relapse.
- |||||||||| fentanyl citrate / Generic mfg.
Fentanyl seeking is attenuated by iboga alkaloid congeners (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10823;
In this study, we report that both 18-MC and Cath decrease fentanyl seeking during prolonged abstinence in both males and females. These results add evidence to the existing literature that iboga alkaloids may be a promising class of compounds for novel pharmacotherapeutic treatment of OUD.
- |||||||||| Belsomra (suvorexant) / Merck (MSD)
Reduced polysubstance self-administration and stress-induced reinstatement following systemic or central amygdala hypocretin-receptor blockade in rats (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10806;
Few studies, however, have examined the role of combined HCRT-R1/2 on compulsive drug taking behavior, and fewer have examined the role of HCRT in drug-taking behavior involving a combined methamphetamine and fentanyl polysubstance...After escalation, a subset of LgA males and females were systemically administered a HCRT-R1/2 antagonist (suvorexant; SUV, 0 and 30mg/kg) 30 min prior to polysubstance self-administration testing...01). Combined, these results suggest HCRT neurotransmission at both HCRT-R1 and -R2, particularly within the CeA, likely contributes to polysubstance-taking and stress-induced polysubstance-seeking behavior.
- |||||||||| fentanyl citrate / Generic mfg.
Sex-specific efficacy of a dual agonist of GLP-1Rs and Y2Rs in opioid-dependent male and female rats (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10765;
The goal of this study was to determine the efficacy of GEP12, a novel dual GLP-1R/Y2R agonist, to reduce fentanyl self-administration and reinstatement in both male and female rats...Taken together, these results indicate that GEP12 reduces voluntary opioid and taking. Future studies will explore the neural mechanisms underlying the sex-specific effects of GEP12 on opioid taking and work to expand the efficacy of dual agonists in opioid-mediated behaviors.
- |||||||||| fentanyl citrate / Generic mfg.
Sex-specific role of CNIH3 in fentanyl IV self-administration (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10763;
Additionally, we use viral approaches to determine the necessity of CNIH3 in the dorsal hippocampus for opioid-seeking behavior. This study, the first to identify sex-specific effects of the AMPAR auxiliary protein CNIH3 on opioid-seeking, begins to uncover the role of CNIH3 on sexually dimorphic AMPAR-dependent behavior and hippocampal synaptic plasticity.
- |||||||||| fentanyl citrate / Generic mfg.
Parallel dopamine circuits from the VTA to Nucleus Accumbens and their response to natural rewards and opioids (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10671;
Our c-Fos experiments extended previous findings, as medial accumbens-projecting DA neurons had significantly higher c-Fos activation as compared to lateral accumbens-projecting DA neurons after a single fentanyl dose. Fentanyl also increased accumbens DA differentially between animals, but further analysis is required to correlate these differences with anatomical location.
- |||||||||| fentanyl citrate / Generic mfg.
Neuronal activation by cocaine varies across molecularly-defined subpopulations of VTA dopamine neurons (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9630;
Notably, fentanyl administration (or co-administration of fentanyl and cocaine) elevated Fos mRNA in both DA subpopulations. These results suggest that two subpopulations of DAergic cells in the VTA respond to cocaine in unique ways and may in turn drive distinct downstream effects and behavioral responses to cocaine.
- |||||||||| fentanyl citrate / Generic mfg.
Chst9 marks a spatially and transcriptionally unique population of Oprm1-expressing neurons in the nucleus accumbens (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9629;
To define the opioid-induced transcriptional activation profile of this population, we injected rats with saline or fentanyl (n = 8, 4M/4F) and used FISH to probe sections for Fos, an immediate early gene expressed in response to neuronal activation...Together, these results identify a spatially and transcriptionally distinct NAc neuron population characterized by the expression of Chst9. The abundant expression of Oprm1 in this population and the conservation of these cells across species suggests that they may play a conserved functional role in opioid response and identify this subpopulation as a target for further investigation.
- |||||||||| fentanyl citrate / Generic mfg.
Xylazine effects on opioid-induced brain hypoxia (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9479;
In this study, we examined the brain-specific hypothermic and hypoxic effects of xylazine and its mixtures with fentanyl and heroin in freely moving rats...The xylazine-heroin mixture strongly potentiated the initial oxygen decrease, and the pattern lacked the hyperoxic portion of the biphasic oxygen response, suggesting more robust and prolonged brain hypoxia. These findings suggest that xylazine exacerbates the life-threatening effects of opioids, proposing worsened brain hypoxia as the mechanism contributing to xylazine-positive opioid-overdose deaths.
- |||||||||| fentanyl citrate / Generic mfg.
The role of the Locus Coeruleus in context-dependent respiratory tolerance to opioids (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9473;
We developed a murine model of context-based repeat fentanyl use where breathing was measured by unrestrained whole-body plethysmography...A failure to establish such associations and the corresponding activity of the LC may increase vulnerability to opioid overdose among chronic opioid users. This work was Supported By R01 DA057767 and R01 HL163965.
- |||||||||| fentanyl citrate / Generic mfg.
Calcium imaging of central amygdala activity after escalation of fentanyl self-administration (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9471;
These results suggest that prior fentanyl self-administration exposure did not alter baseline CeA activity but decreased CeA reactivity to fentanyl. Further work is needed to determine whether these tolerance-like changes in CeA calcium activity persevere throughout extended abstinence.
- |||||||||| fentanyl citrate / Generic mfg.
Transcriptomic analysis reveals altered hippocampal neuronal function and glial cell responses following sub-chronic exposure to fentanyl (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9470;
Fentanyl, like morphine, binds to mu-opioid receptors (MOR) in many brain regions, and this binding event can lead to addiction, tolerance, impairment of cognitive functions, and inhibit nociception, arousal, and respiration. Additional bulk RNA-seq experiments revealed that 44 of these 314 genes (e. g. , Rph3a, Unc13c, Dnmt3a and Ntng2) were also down-regulated in fentanyl-treated (40
- |||||||||| naloxone injection / Generic mfg., fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Parabrachial-to-amygdala circuits associated with opioid withdrawal (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9463;
Opioids, such as morphine and fentanyl, induce robust analgesic and euphoric effects, but chronic use induces strong opioid dependence...Mice received double daily injections of morphine over 5 days, then withdrawal was induced by the injection of naloxone...These results indicates that PBN afferents are critical for the activation of CEC during withdrawal and contribute to the aversive effects induced by opioid withdrawal. Future study will examine the contributions of more specific neural populations within the PBN, including mu-opioid receptor- and CGRP-expressing neurons.
- |||||||||| fentanyl citrate / Generic mfg.
Striatal cholinergic interneurons influence fentanyl seeking (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9455;
For the chemogenetic study, preliminary results suggest that excitation of NAc shell CINs does not influence fentanyl consumption. Together, our results suggest that cholinergic neurons may be involved in aversion-resistant opioid seeking and consumption.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Pharmacological characterization of (R)-ketamine at the mu-opioid receptor: implications for abuse liability (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_9431;
Finally, we assessed the physiological and behavioral consequences of repeated exposure to IVSA-relevant doses of (R)-ketamine on MOR density (using autoradiography) and sensitivity (using [35S]GTP?S), and subsequent heroin self-administration behavior. The results from these experiments will be important to better understand the potential consequences of using (R)-ketamine as a treatment for depression.
- |||||||||| fentanyl citrate / Generic mfg.
Traumatic brain injury with coma, neurocritical care, and recovery in swine (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_8868;
After probes were placed and subjects were stable, total intravenous anesthesia with propofol/fentanyl was initiated and isoflurane was shut off...A large animal model replicating the mechanisms and manifestations of human TBI is essential to bridge the translational gap between rodent studies and clinical trials. This paradigm further increases translational relevance and allows for preclinical study of neurocritical care, while extending the study period for moderate-to-severe TBI with coma.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
A Comparative Examination of Morphine and Fentanyl: Unraveling the Differential Impacts on Breathing and Airway Stability (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_7769;
Finally, we found that fentanyl-exposed mice had reduced survival under hypoxic conditions compared to mice given morphine, demonstrating that fentanyl becomes more lethal in the context of hypoxemia. Our findings shed light on the distinct and profound impacts of these opioids on respiration and airway stability and lay the foundation for improved opioid use guidelines and more effective OIRD prevention strategies.
- |||||||||| fentanyl citrate / Generic mfg.
Beta-adrenergic receptor blockade persistently disrupts retrieval of fentanyl-associated memory (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_6657;
These investigations are underway to determine the specific brain regions common to addiction-retrieval pathways across drug classes. Overall, these findings suggest a widespread therapeutic use for propranolol in the treatment of addiction through prevention of drug-associated memory retrieval to reduce cue-elicited drug seeking and relapse.
- |||||||||| fentanyl citrate / Generic mfg.
Intravenous fentanyl self-administration in genetically diverse mice (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_6644;
Collectively, these observations underscore that genetic diversity is necessary to capture the phenotypic diversity that, at its extremes, represents vulnerability and resistance to addiction-like fentanyl taking and seeking. Moreover, the high heritability of the measured intravenous fentanyl self-administration behaviors reveals that recombinant inbred mouse panels can be used to discover and dissect the genetic underpinning of the distinct phenotypes that, together, drive fentanyl addiction.
- |||||||||| fentanyl citrate / Generic mfg.
Investigation of Peripheral Mechanisms Underlying Opioid-Induced Respiratory Depression (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_3841;
Synthetic opioid opioid-related overdose deaths continue to rise, thus it is critical to understand the mechanisms by which fentanyl induces respiratory depression...Rats displayed an aversion to the naloxone-paired side, and this was not observed in NLXM-treated rats. These findings provide insight into peripheral mechanisms that contribute to OIRD and how antagonism of these receptors could be a promising therapeutic strategy for managing OIRD by sparing the CNS-driven acute opioid withdrawal generally observed with the use of naloxone.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
The orphan receptor GPR139 modulates cholinergic activity in the striatum (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_3711;
Further, consistent with an increase in cholinergic activity we observe that activation of Smo counteracts place preference formation. We are currently investigating whether Smo and GPR139 pharmacology alter reciprocal release dynamics of DA and ACh.
- |||||||||| fentanyl citrate / Generic mfg., methadone / Generic mfg.
Mu opioid receptor activation does not activate hiv provirus transcription in a microglia model of latent hiv infection (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_2228;
Together, these results suggest that in our model of HIV infection in microglia, opioids that act on mu opioid receptors do not increase transcription of HIV. Therefore, we suggest that commonly prescribed and abused opioids do not enhance activation of transcription of HIV, indicating that therapy with methadone might be a suitable avenue for treating addiction in people living with HIV.
- |||||||||| fentanyl citrate / Generic mfg.
Tachykinin-1-expressing neurons mediate opioid-induced respiratory depression (WCC 147A) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_1069;
4586) in Tac1-Oprm1-/- mice between saline and fentanyl treatments. Taken together, our results show that the absence of functional MORs in Tac1-expressing neurons alleviates respiratory depression by the opioid fentanyl, suggesting that these cells may mediate the respiratory side-effects of opioids.
- |||||||||| fentanyl citrate / Generic mfg.
Opioids alter the laryngeal adductor reflex to superior laryngeal nerve stimulation (WCC 152A) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_710;
Furthermore, increased use of opioids, such as codeine and fentanyl, can affect the coordination and response character of LAR...These results support central actions of some opioids on the LAR. Further, they suggest the participation of complex opioid-sensitive circuits in the recruitment patterns of laryngeal adductor muscle motor units during LAR behavior.
- |||||||||| hydromorphone IR (PFR03321) / Ensysce Biosciences, hydromorphone (PF329) / Ensysce Biosciences, Instanyl (fentanyl) / Takeda
Standardized Clinical Pathways Improve Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2760;
Our goal of increased percentage of patients receiving pain medication within 30 minutes and decreased time to first analgesic was not achieved, however this is an ongoing project and with education in implementation of the clinical pathway we hope to continue to see long term progress. Additionally, in the future, we plan to expand use of this pathway to additional sites within our health care system.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
36-Month Follow-up Results of the Gimema (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2333;
The updated data from the VERITAS trial show that in young and fit patients with adverse genetic characteristics the front-line VenR combination was an effective regimen with high rates of deep responses with uMRD. Furthermore, at 33 months from the EOT, uMRD was maintained in the PB and BM in about half of the patients.
- |||||||||| fentanyl citrate / Generic mfg.
Review, Journal: Xylazine Adulteration of the Heroin-Fentanyl Drug Supply : A Narrative Review. (Pubmed Central) - Nov 1, 2023
Clinical experience along with the available pertinent research were used to review xylazine adulteration of the drug supply and provide guidance on the care of patients exposed to xylazine. This review discusses xylazine pharmacology, animal and human clinical effects, and what is known to date about care of patients experiencing acute overdose, xylazine-fentanyl withdrawal, and xylazine-associated wounds.
- |||||||||| fentanyl citrate / Generic mfg., isoflurane / Generic mfg.
Journal, Surgery: The effect of erector spinae plane block on the use of anesthetic medications in lumbar spine surgery. (Pubmed Central) - Oct 31, 2023
This review discusses xylazine pharmacology, animal and human clinical effects, and what is known to date about care of patients experiencing acute overdose, xylazine-fentanyl withdrawal, and xylazine-associated wounds. ESPB under ultrasound guidance is an effective method of regional anesthesia/analgesia for lumbar spine surgery (fusion) by decreasing the consumption of anesthetics during and following the surgery.
- |||||||||| fentanyl citrate / Generic mfg., methadone / Generic mfg.
Journal: Research Priorities for Expansion of Opioid Use Disorder Treatment in the Community Pharmacy. (Pubmed Central) - Oct 30, 2023
In the last decade, the U.S. opioid overdose crisis has magnified, particularly since the introduction of synthetic opioids, including fentanyl...Specific topics for research included adaptation of pharmacy infrastructure for clinical service provision, strategies for interprofessional collaboration including health service models, drug policy and regulation, pharmacist education about OUD and OUD treatment, including didactic, experiential, and interprofessional curricula, and educational interventions to reduce stigma towards this patient population. Together, expanding these research areas can bring effective MOUD to where it is most needed.
- |||||||||| fentanyl citrate / Generic mfg., ketorolac / Generic mfg.
Clinical, Review, Journal: Effectiveness of Intranasal Analgesia in the Emergency Department. (Pubmed Central) - Oct 28, 2023
Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. Intravenous is simple to administer, non-invasive, rapid onset, and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management.
- |||||||||| fentanyl citrate / Generic mfg.
Journal: "As safe as possible": a qualitative study of opioid withdrawal and risk behavior among people who use illegal opioids. (Pubmed Central) - Oct 28, 2023
However, theories that position activities taken to avoid withdrawal as irrational and as evidence of pathology are poorly aligned with the complexity of PWUIO's actual lives. We recommend the use of less deterministic and less medicalized theories of risk that better account for differences between how people view the world, and for the role of socio-structural forces in the production of risk.
- |||||||||| fentanyl citrate / Generic mfg.
Journal: The Drug Overdose Epidemic in the U.S.-Mexico Border Region: Shifts, Progression, and Community Characteristics. (Pubmed Central) - Oct 27, 2023
Previous studies show the reach of the current drug overdose epidemic into the U.S.-Mexico border region, albeit with a unique border-specific wave pattern compared to national waves and a delayed onset of fentanyl involvement (Wave I: 2002-2011, Wave II: 2012-2016, and Wave III: since 2017)...Findings suggest that more disadvantaged U.S.-Mexico border communities may encounter increasing rates of overdose death over the coming years. Interventions need to target not only the supply side but also the underlying social root causes for sustainable overdose prevention.
|
