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https://www.readbyqxmd.com/read/28649993/kappa-opioid-receptor-activation-in-dopamine-neurons-disrupts-behavioral-inhibition
#1
Antony D Abraham, Harrison M Fontaine, Allisa J Song, Mackenzie M Andrews, Madison A Baird, Brigitte L Kieffer, Benjamin B Land, Charles Chavkin
The dynorphin/kappa opioid receptor (KOR) system has been previously implicated in the regulation of cognition, but the neural circuitry and molecular mechanisms underlying KOR-mediated cognitive disruption are unknown. Here, we used an operational test of cognition involving timing and behavioral inhibition and found that systemic KOR activation impairs performance of male and female C57BL/6 mice in the differential reinforcement of low response rates (DRL) task. Systemic KOR antagonism also blocked stress-induced disruptions of DRL performance...
June 26, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28642282/kappa-opioid-receptors-mediate-heterosynaptic-suppression-of-hippocampal-inputs-in-the-rat-ventral-striatum
#2
Julie Brooks, Patricio O'Donnell
Kappa opioid receptors (KOR) are highly enriched within the ventral striatum (VS) and are thought to modulate striatal neurotransmission. This includes presynaptic inhibition of local glutamatergic release from excitatory inputs to the VS. However, it is not known which inputs drive this modulation and what impact they have on the local circuit dynamics within the VS. Individual medium spiny neurons (MSNs) within the VS serve as a site of convergence for glutamatergic inputs arising from the prefrontal cortex (PFC) and limbic regions, such as the hippocampus (HP)...
June 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28637770/analgesia-and-opioids-a-pharmacogenetics-shortlist-for-implementation-in-clinical-practice
#3
REVIEW
Maja Matic, Saskia N de Wildt, Dick Tibboel, Ron H N van Schaik
BACKGROUND: The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly...
June 21, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28635181/buprenorphine-requires-concomitant-activation-of-nop-and-mop-receptors-to-reduce-cocaine-consumption
#4
Marsida Kallupi, Qianwei Shen, Giordano de Guglielmo, Dennis Yasuda, V Blair Journigan, Nurulain T Zaveri, Roberto Ciccocioppo
Buprenorphine's clinical use is approved for the treatment of heroin addiction; however, evidence supporting its efficacy in cocaine abuse also exists. While for heroin it has been demonstrated that the effect of buprenorphine is mediated by its ability to activate μ-opioid peptide receptor (MOP) receptors, the mechanism through which it attenuates cocaine intake remains elusive. We explored this mechanism using operant models where rodents were trained to chronically self-administer cocaine for 2 hours daily...
June 21, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28625549/the-long-term-effects-of-stress-and-kappa-opioid-receptor-activation-on-conditioned-place-aversion-in-male-and-female-california-mice
#5
Abigail R Laman-Maharg, Tiffany Copeland, Evelyn Ordoñes Sanchez, Katharine L Campi, Brian C Trainor
Psychosocial stress leads to the activation of kappa opioid receptors (KORs), which induce dysphoria and facilitate depression-like behaviors. However, less is known about the long-term effects of stress and KORs in females. We examined the long-term effects of social defeat stress on the aversive properties of KOR activation in male and female California mice (Peromyscus californicus) using a conditioned place aversion paradigm. Female California mice naïve to social defeat, formed a place aversion following treatment with 2...
June 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28589966/role-of-kappa-opioid-receptors-in-the-bed-nucleus-of-stria-terminalis-in-reinstatement-of-alcohol-seeking
#6
A D Lê, Douglas Funk, Kathleen Coen, Sahar Tamadon, Yavin Shaham
Kappa opioid receptors (KORs) and their endogenous ligand dynorphin are involved in stress-induced alcohol seeking but the mechanisms involved are largely unknown. We previously showed that systemic injections of the KOR agonist U50,488, which induce stress-like aversive states, reinstate alcohol seeking after extinction of the alcohol-reinforced responding. Here, we used the neuronal activity marker Fos and site-specific injections of the KOR antagonist nor-BNI and U50,488 to study brain mechanisms of U50,488-induced reinstatement of alcohol seeking...
June 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28588463/looking-for-the-self-phenomenology-neurophysiology-and-philosophical-significance-of-drug-induced-ego-dissolution
#7
Raphaël Millière
There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as "drug-induced ego dissolution (DIED)", for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR)...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28567699/effects-of-nalfurafine-on-the-reinforcing-thermal-antinociceptive-and-respiratory-depressant-effects-of-oxycodone-modeling-an-abuse-deterrent-opioid-analgesic-in-rats
#8
E Andrew Townsend, Jennifer E Naylor, S Stevens Negus, Shelley R Edwards, Hina N Qureshi, Hunter W McLendon, Christopher R McCurdy, Coco N Kapanda, Jussara M do Carmo, Fernanda S da Silva, John E Hall, Kenneth J Sufka, Kevin B Freeman
RATIONALE: Strategies to reduce the misuse of mu opioid agonists are critically needed. Previous work has shown that kappa opioid agonists can diminish the abuse-related effects and augment the antinociceptive effects of mu agonists. However, use of traditional kappa agonists is limited by their dysphoric side effects. OBJECTIVES: The current study examined the effects of nalfurafine, a clinically available atypical kappa agonist, on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone in male rats...
May 31, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28554003/opioids-and-opioid-receptors-orchestrate-wound-repair
#9
Ying Wang, Mihir Gupta, Tasneem Poonawala, Mariya Farooqui, Yunfang Li, Fei Peng, Sheldon Rao, Michael Ansonoff, John E Pintar, Kalpna Gupta
We have previously shown that topical opioids including morphine and its congeners promote healing of full thickness ischemic wounds in rats. We examined the contribution of mu opioid receptor (MOPr)-mediated healing of full thickness ischemic wounds using MOPr and delta or kappa opioid receptor knockout (KO) mice. Wound closure in the early (day 5) as well as later phases was delayed in topical morphine or PBS-treated MOPr-KO mice compared with reciprocal treatments of wounds in wild-type (WT) mice. MOPr expression was significantly upregulated at 30 min in the wound margins and colocalized with wound margins and vasculature in the epidermal and dermal layers of the skin...
May 18, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28550455/-effects-of-the-novel-relatively-short-acting-kappa-opioid-receptor-antagonist-ly2444296-in-behaviors-observed-after-chronic-extended-access-cocaine-self-administration-in-rats
#10
Marta Valenza, Eduardo R Butelman, Mary Jeanne Kreek
RATIONALE: The recruitment of the stress circuitry contributes to a shift from positive to negative reinforcement mechanisms sustaining long-term cocaine addiction. The kappa opioid receptor (KOPr) signaling is upregulated by stress and chronic cocaine exposure. While KOPr agonists induce anhedonia and dysphoria, KOPr antagonists display antidepressant and anxiolytic properties. Most of the knowledge on KOPr antagonism is based on drugs with unusual pharmacokinetic and pharmacodynamic properties, complicating interpretation of results...
May 27, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28541028/correction-to-structure-activity-relationship-studies-of-functionally-selective-kappa-opioid-receptor-agonists-that-modulate-erk-1-2-phosphorylation-while-preserving-g-protein-over-%C3%AE-arrestin2-signaling-bias
#11
Kimberly M Lovell, Kevin J Frankowski, Edward L Stahl, Stephen R Slauson, Euna Yoo, Thomas E Prisinzano, Jeffrey Aubé, Laura M Bohn
No abstract text is available yet for this article.
May 25, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28536865/the-c-2-derivatives-of-salvinorin-a-ethoxymethyl-ether-sal-b-and-%C3%AE-tetrahydropyran-sal-b-have-anti-cocaine-properties-with-minimal-side-effects
#12
Amy W M Ewald, Peter J Bosch, Aimee Culverhouse, Rachel Saylor Crowley, Benjamin Neuenswander, Thomas E Prisinzano, Bronwyn M Kivell
RATIONALE: Kappa-opioid receptor (KOPr) agonists have pre-clinical anti-cocaine and analgesic effects. However, side effects including sedation, dysphoria, aversion, anxiety and depression limit their therapeutic development. The unique structure of salvinorin A has been used to develop longer acting KOPr agonists. OBJECTIVES: We evaluate two novel C-2 analogues of salvinorin A, ethoxymethyl ether Sal B (EOM Sal B) and β-tetrahydropyran Sal B (β-THP Sal B) alongside U50,488 for their ability to modulate cocaine-induced behaviours and side effects, pre-clinically...
May 23, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28531297/mechanisms-of-kappa-opioid-receptor-potentiation-of-dopamine-d2-receptor-function-in-quinpirole-induced-locomotor-sensitization-in-rats
#13
Angélica P Escobar, Marcela P González, Rodrigo C Meza, Verónica Noches, Pablo Henny, Katia Gysling, Rodrigo A España, José A Fuentealba, María E Andrés
Background: Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of Quinpirole (QNP), a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist (KOR). The mechanism underlying KOR potentiation of QNP-induced locomotor sensitization remains to be elucidated...
May 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28509375/chronic-nicotine-induced-changes-in-gene-expression-of-delta-and-kappa-opioid-receptors-and-their-endogenous-ligands-in-the-mesocorticolimbic-system-of-the-rat
#14
Muzeyyen Ugur, Egemen Kaya, Oguz Gozen, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. The present study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4 or 0.6 mg/kg/day for six days. Rats were decapitated one hour after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system...
May 16, 2017: Synapse
https://www.readbyqxmd.com/read/28502907/neuropathic-and-inflammatory-antinociceptive-effects-and-electrocortical-changes-produced-by-salvia-divinorum-in-rats
#15
Karina Simón-Arceo, Ma Eva González-Trujano, Ulises Coffeen, Rodrigo Fernández-Mas, Francisco Mercado, Angélica Almanza, Bernardo Contreras, Orlando Jaimes, Francisco Pellicer
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists. AIM OF THE STUDY: Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats...
May 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28501425/the-effects-of-kratom-on-restraint-stress-induced-analgesia-and-its-mechanisms-of-action
#16
José Luis Vázquez López, Lorenz Schild, Thomas Günther, Stefan Schulz, Hartmud Neurath, Axel Becker
ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa and its extracts are called kratom (dried leaves, extract). They contain several alkaloids with an affinity for different opioid receptors. They are used in traditional medicine for the treatment of different diseases, as a substitute by opiate addicts, and to mitigate opioid withdrawal symptoms. Apart from their medical properties, they are used to enhance physical endurance and as a means of overcoming stress. PURPOSE: The aim of this study was to determine the mechanisms underlying the effects of kratom on restraint-stress-induced analgesia which occurs during or following exposure to a stressful or fearful stimulus...
May 10, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28496466/validated-spectrophtometric-method-for-simultaneous-determination-of-buprenorphine-and-naloxone-in-pharmaceutical-dosage-forms
#17
Effat Souri, Farzaneh Sadat Ahmadi, Maliheh Barazandeh Tehrani, Majid Mohammad Hosseini, Sedigheh Fadaye Vatan
Buprenorphine is a partial mu agonist and kappa antagonist which is used for the treatment of pain and opioid addiction. A mixture of buprenorphine hydrochloride and naloxone hydrochloride has been approved for the treatment of opioid dependence. In this study a third order derivative spectrophotometric method based on zero-crossing technique has been used for the simultaneous determination of buprenorphine hydrochloride and naloxone hydrochloride in tablets. The measurements were carried out at wavelengths of 257...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28475363/new-tetranorlabdanoic-acid-from-aerial-parts-of-salvia-aethiopis
#18
Radhakrishnan Srivedavyasasri, Miriah B White, Tatyana S Kustova, Nadezhda G Gemejiyeva, Charles L Cantrell, Samir A Ross
Salvia aethiopis is a perennial plant native to Eurasia and known by the common names Mediterranean sage or African sage. This plant has been used in Iranian medicine as a carminative and tonic. The ethanolic extract of aerial part of S. aethiopis exhibited moderate to weak activity towards delta and kappa opioid receptors (46.3 and 45.3% displacement, respectively). Chromatographic purification of the ethanolic extract on silica gel column led to isolation of one new: 3α-hydroxy-8α-acetoxy-13,14,15,16-tetranorlabdan-12-oic acid (I) and three known compounds: sesquiterpene spathulenol (II), β-sitosterol (III) and β-sitosterol-3-O-glucoside (IV)...
May 5, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28464209/alanine-scan-of-the-opioid-peptide-dynorphin-b-amide
#19
Anand A Joshi, Thomas F Murray, Jane V Aldrich
To date structure-activity relationship (SAR) studies of the dynorphins (Dyn), endogenous peptides for kappa opioid receptors (KOR), have focused almost exclusively on Dyn A with minimal studies on Dyn B. While both Dyn A and Dyn B have identical N-terminal sequences, their C-terminal sequences differ which could result in differences in pharmacological activity. We performed an alanine scan of the non-glycine residues up through residue 11 of Dyn B amide to explore the role of these side chains in the activity of Dyn B...
May 2, 2017: Biopolymers
https://www.readbyqxmd.com/read/28455226/the-effect-of-selective-opioid-receptor-agonists-and-antagonists-on-epileptiform-activity-in-morphine-dependent-infant-mice-hippocampal-slices
#20
Yousef Panahi, Ehsan Saboory, Ali Rassouli, Goudarz Sadeghi-Hashjin, Shiva Roshan-Milani, Leila Derafshpour, Yousef Rasmi
Hippocampal slices of mouse brain were used to estimate how selective agonist and antagonist of opioid receptors alter Low-Mg(+2) artificial cerebrospinal fluid (LM-ACSF)-induced epileptiform activities in normal and morphine-dependent mice. Brain slices were obtained from control and morphine-dependent mice. The morphine-dependent group received morphine once a day for 5 consecutive days, and the control group received saline. All injections were administered subcutaneously (s.c) in a volume of 0.1mL on postnatal days 14-18...
August 2017: International Journal of Developmental Neuroscience
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