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  1. Article ; Online: Effect of prenatal and early post-natal oxycodone exposure on the reinforcing and antinociceptive effects of oxycodone in adult C57BL/6 J mice.

    Zhang, Yong / Butelman, Eduardo R / Kreek, Mary Jeanne

    Psychopharmacology

    2023  Volume 241, Issue 2, Page(s) 359–377

    Abstract: Abuse of opioids (mu-opioid agonists such as oxycodone) among parents during the gestation and early post-natal period is a concern for the long-term health of the offspring, beyond potential neonatal withdrawal symptoms. However, there is only limited ... ...

    Abstract Abuse of opioids (mu-opioid agonists such as oxycodone) among parents during the gestation and early post-natal period is a concern for the long-term health of the offspring, beyond potential neonatal withdrawal symptoms. However, there is only limited information on such effects.
    Objectives: We examined how prenatal, and early-post natal oxycodone exposure affected opioid addiction behaviors.
    Methods: Adult male and female C57BL/CJ mice housed separately were first injected with ascending doses of oxycodone 1 time/day (1 mg/kg × 10 days, 1.5 mg/kg × 10 days, 2 mg/kg × 10 days, s.c.) whereas control mice were injected with saline. Newly formed parental dyads were then housed together and continued to receive ascending doses of oxycodone (3 mg/kg × 10 days, 4 mg/kg × 10 days, 5 mg/kg × 10 days, 6 mg/kg × 10 days or saline, s.c.) or saline during mating and gestation until the birth of the litter. The dams continued to receive oxycodone or saline through lactation, until F1 offspring were weaned. Upon reaching adulthood (12 weeks of age), male and female F1 offspring were examined in intravenous self-administration (IVSA) of oxycodone, on oxycodone-induced conditioned place preference (CPP) and oxycodone-induced antinociception.
    Results: Adult F1 male and female offspring of parental dyads exposed to oxycodone self-administered more oxycodone, compared to offspring of control parental dyads. Ventral and dorsal striatal mRNA levels of genes such as Fkbp5 and Oprm1 were altered following oxycodone self-administration.
    Conclusion: Prenatal and early post-natal oxycodone exposure enhanced oxycodone self-administration during adulthood in the C57BL/6 J mice.
    MeSH term(s) Pregnancy ; Male ; Female ; Mice ; Animals ; Oxycodone/pharmacology ; Mice, Inbred C57BL ; Analgesics, Opioid/pharmacology ; Opioid-Related Disorders ; Conditioning, Classical
    Chemical Substances Oxycodone (CD35PMG570) ; Analgesics, Opioid
    Language English
    Publishing date 2023-12-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 130601-7
    ISSN 1432-2072 ; 0033-3158
    ISSN (online) 1432-2072
    ISSN 0033-3158
    DOI 10.1007/s00213-023-06493-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Genetic Vulnerability to Opioid Addiction.

    Reed, Brian / Kreek, Mary Jeanne

    Cold Spring Harbor perspectives in medicine

    2021  Volume 11, Issue 6

    Abstract: Opioid addiction, also referred to as opioid use disorder, continues to be a devastating problem throughout the world. Familial relation and twin studies have revealed opioid addiction, like other addictive diseases, to be profoundly influenced by ... ...

    Abstract Opioid addiction, also referred to as opioid use disorder, continues to be a devastating problem throughout the world. Familial relation and twin studies have revealed opioid addiction, like other addictive diseases, to be profoundly influenced by genetics. Genetics studies of opioid addiction have affirmed the importance of genetics contributors in susceptibility to develop opioid addiction, and also have important implications on treatment for opioid addiction. But the complexity of the interactions of multiple genetic variants across diverse genes, as well as substantial differences in allelic frequencies across populations, thus far limits the predictive value of individual genetics variants.
    MeSH term(s) Behavior, Addictive/genetics ; Gene Frequency ; Genetic Variation ; Humans ; Opioid-Related Disorders/genetics
    Language English
    Publishing date 2021-06-01
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2157-1422
    ISSN (online) 2157-1422
    DOI 10.1101/cshperspect.a039735
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  3. Article ; Online: Blockade of alcohol excessive and "relapse" drinking in male mice by pharmacological cryptochrome (CRY) activation.

    Zhou, Yan / Kreek, Mary Jeanne

    Psychopharmacology

    2021  Volume 238, Issue 4, Page(s) 1099–1109

    Abstract: Rationale: Metabolic dysfunction, mood disorders, anxiety disorders, and substance abuse disorders are associated with disruptions in circadian rhythm and circadian clock gene machinery. While the effects of alcohol on several core components of the ... ...

    Abstract Rationale: Metabolic dysfunction, mood disorders, anxiety disorders, and substance abuse disorders are associated with disruptions in circadian rhythm and circadian clock gene machinery. While the effects of alcohol on several core components of the clock genes have been described in rodent models, pharmacological activation or inhibition of clock gene functions has not been studied on alcohol drinking behaviors.
    Objectives: We investigated whether cryptochrome (CRY1/2) activator KL001 altered alcohol intake in mice in excessive and relapse-like alcohol drinking models.
    Methods: Mice, subjected to 3 weeks of chronic intermittent alcohol drinking (IAD) (two-bottle choice, 24-h access every other day) developed excessive alcohol intake and high preference. We evaluated the pharmacological effects of KL001 after either 1-day acute withdrawal from IAD or 1-week chronic withdrawal using the alcohol deprivation effect (ADE) model.
    Results: Single pretreatment with KL001 at 1-4 mg kg
    Conclusions: Pretreatment with KL001 (a CRY1/2 activator) reduces excessive and "relapse" alcohol drinking in mice. Our in vivo results with a CRY activator suggest a possible novel target for alcohol treatment intervention.
    MeSH term(s) Animals ; Male ; Mice ; Alcohol Drinking/psychology ; Alcoholism/prevention & control ; Carbazoles/pharmacology ; Central Nervous System Depressants/blood ; Cryptochromes/agonists ; Cryptochromes/drug effects ; Dose-Response Relationship, Drug ; Drug Tolerance ; Enzyme Activation/drug effects ; Ethanol/blood ; Mice, Inbred C57BL ; Recurrence ; Substance Withdrawal Syndrome/drug therapy ; Substance Withdrawal Syndrome/psychology ; Sulfonamides/pharmacology
    Chemical Substances Carbazoles ; Central Nervous System Depressants ; Cryptochromes ; Ethanol (3K9958V90M) ; KL001 ; Sulfonamides
    Language English
    Publishing date 2021-01-08
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 130601-7
    ISSN 1432-2072 ; 0033-3158
    ISSN (online) 1432-2072
    ISSN 0033-3158
    DOI 10.1007/s00213-020-05757-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Impact of OPRM1 (Mu-opioid Receptor Gene) A112G Polymorphism on Dual Oxycodone and Cocaine Self-administration Behavior in a Mouse Model.

    Zhang, Yong / Randesi, Matthew / Blendy, Julie A / Kreek, Mary Jeanne / Butelman, Eduardo R

    Neuroscience

    2024  Volume 539, Page(s) 76–85

    Abstract: The use of mu-opioid receptor (MOP-r) agonists such as oxycodone together with cocaine is prevalent, and deaths attributed to using these combinations have increased.: Rationale: It is unknown if functional single nucleotide polymorphisms (SNPs), such ...

    Abstract The use of mu-opioid receptor (MOP-r) agonists such as oxycodone together with cocaine is prevalent, and deaths attributed to using these combinations have increased.
    Rationale: It is unknown if functional single nucleotide polymorphisms (SNPs), such as the OPRM1 (MOP-r gene) SNP A118G, can predispose individuals to more dual opioid and psychostimulant intake. The dual self-administration (SA) of MOP-r agonists and cocaine has not been thoroughly examined, especially with regard to neurobiological changes.
    Objectives: We examined oxycodone SA and subsequent dual oxycodone and cocaine SA in male and female A112G (A/G and G/G, heterozygote and homozygote, respectively) mice, models of human A118G carriers, versus wild-type (A/A) mice.
    Methods: Adult male and female A/G, G/G and A/A mice self-administered oxycodone (0.25 mg/kg/infusion, 4hr/session, FR 1.) for 10 consecutive days (sessions 1-10). Mice then self-administered cocaine (2 hr) following oxycodone SA (4 hr, as above) in each session for a further 10 consecutive days (sessions 11-20). Message RNA transcripts of 24 reward-related genes were examined in the dorsal striatum.
    Results: Male and female A/G and G/G mice had greater oxycodone SA than A/A mice did in the initial 10 days and in the last 10 sessions. Further, A/G and G/G mice showed greater cocaine intake than A/A mice. Dorsal striatal mRNA levels of Pdyn, Fkbp5, Oprk1, and Oprm1 were altered following oxycodone and cocaine SA.
    Conclusions: These studies demonstrated that this functional genetic variation in Oprm1 affected dual opioid and cocaine SA and altered specific gene expression in the striatum.
    MeSH term(s) Adult ; Male ; Female ; Humans ; Mice ; Animals ; Oxycodone/pharmacology ; Analgesics, Opioid ; Polymorphism, Single Nucleotide ; Cocaine/pharmacology ; Receptors, Opioid ; Receptors, Opioid, mu/genetics ; Receptors, Opioid, mu/metabolism
    Chemical Substances Oxycodone (CD35PMG570) ; Analgesics, Opioid ; Cocaine (I5Y540LHVR) ; Receptors, Opioid ; Receptors, Opioid, mu ; OPRM1 protein, human
    Language English
    Publishing date 2024-01-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 196739-3
    ISSN 1873-7544 ; 0306-4522
    ISSN (online) 1873-7544
    ISSN 0306-4522
    DOI 10.1016/j.neuroscience.2024.01.002
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  5. Article ; Online: Review of addiction risk potential associated with adolescent opioid use.

    Windisch, Kyle A / Kreek, Mary Jeanne

    Pharmacology, biochemistry, and behavior

    2020  Volume 198, Page(s) 173022

    Abstract: Adolescence is a critical period of development with robust behavioral, morphological, hormonal, and neurochemical changes including changes in brain regions implicated in the reinforcing effects of drugs such as opioids. Here we examine the preclinical ... ...

    Abstract Adolescence is a critical period of development with robust behavioral, morphological, hormonal, and neurochemical changes including changes in brain regions implicated in the reinforcing effects of drugs such as opioids. Here we examine the preclinical and, where appropriate complementary clinical literature, for the behavioral and neurological changes induced by adolescent opioid exposure/use and their long-term consequences during adulthood. Adolescent opioid exposure results in a widened biphasic shift in reinforcement with increased impact of positive rewarding aspects during initial use and profound negative reinforcement during adulthood. Females may have enhanced vulnerability due to fast onset of antinociceptive tolerance and reduced severity of somatic withdrawal symptoms during adolescence. Overall, adolescent opioid exposure, be it legally prescribed protracted intake or illicit consumption, results in significant and prolonged consequences of increased opioid reward concomitant with reduced analgesic efficacy and exacerbated somatic withdrawal severity during opioid use/exposure in adulthood. These findings are highly relevant to physicians, parents, law makers, and the general public as adolescent opioid exposure/misuse results in heightened risk for substance use disorders.
    MeSH term(s) Adolescent ; Adult ; Analgesics, Opioid/adverse effects ; Analgesics, Opioid/pharmacology ; Animals ; Behavior, Addictive/epidemiology ; Behavior, Addictive/etiology ; Behavior, Animal/drug effects ; Brain/drug effects ; Drug Tolerance ; Female ; Humans ; Locomotion/drug effects ; Male ; Mice ; Opioid-Related Disorders/epidemiology ; Opioid-Related Disorders/etiology ; Rats ; Reinforcement, Psychology ; Reward ; Risk Factors ; Substance Withdrawal Syndrome/epidemiology ; Substance-Related Disorders/epidemiology
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2020-08-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 191042-5
    ISSN 1873-5177 ; 0091-3057
    ISSN (online) 1873-5177
    ISSN 0091-3057
    DOI 10.1016/j.pbb.2020.173022
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  6. Article ; Online: Population-specific genetic background for the OPRM1 variant rs1799971 (118A>G): implications for genomic medicine and functional analysis.

    Levran, Orna / Kreek, Mary Jeanne

    Molecular psychiatry

    2020  Volume 26, Issue 7, Page(s) 3169–3177

    Abstract: The mu-opioid receptor (MOR, OPRM1) has important roles in diverse functions including reward, addiction, and response to pain treatment. SNP rs1799971 (118A > G, N40D) which occur at a high frequency (40-60%) in Asia and moderate frequency (15%) in ... ...

    Abstract The mu-opioid receptor (MOR, OPRM1) has important roles in diverse functions including reward, addiction, and response to pain treatment. SNP rs1799971 (118A > G, N40D) which occur at a high frequency (40-60%) in Asia and moderate frequency (15%) in samples of European ancestry, is the only common coding variant in the canonical transcript, in non-African populations. Despite extensive studies, the molecular consequences of this variation remained unresolved. The aim of this study was to determine the genetic background of the OPRM1 region of 118G in four representative populations and to assess its potential modulatory effect. Seven common haplotypes with distinct population distribution were identified based on seven SNPs. Three haplotypes carry the 118G and additional highly linked regulatory SNPs (e.g., rs9383689) that could modulate the effect of 118G. Extended analysis in the 1000 Genomes database (n = 2504) revealed a common East Asian-specific haplotype with a different genetic background in which there are no variant alleles for an upstream LD block tagged by the eQTL rs9397171. The major European haplotype specifically includes the eQTL intronic SNP rs62436463 that must have arisen after the split between European and Asian populations. Differentiating between the effect of 118G and these SNPs requires specific experimental approaches. The analysis also revealed a significant increase in two 118A haplotypes with eQTL SNPs associated with drug addiction (rs510769) and obesity (rs9478496) in populations with native Mexican ancestry. Future studies are required to assess the clinical implication of these findings.
    MeSH term(s) Alleles ; Genetic Background ; Genetics, Population ; Genomic Medicine ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Receptors, Opioid, mu/genetics
    Chemical Substances OPRM1 protein, human ; Receptors, Opioid, mu
    Language English
    Publishing date 2020-10-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-020-00902-4
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  7. Article ; Online: Nalfurafine modulates the reinforcing effects of oxycodone in male and female adolescent C57BL/6J mice.

    Zhang, Yong / Kreek, Mary Jeanne

    Neuropharmacology

    2020  Volume 176, Page(s) 108244

    Abstract: Addiction to prescription opioid, such as oxycodone, has affected millions of adolescents and young adults. Kappa opioid receptor (KOP-r) agonist can counterbalance the euphoria effects of mu opioid agonists like oxycodone. Nalfurafine is a KOP-r agonist. ...

    Abstract Addiction to prescription opioid, such as oxycodone, has affected millions of adolescents and young adults. Kappa opioid receptor (KOP-r) agonist can counterbalance the euphoria effects of mu opioid agonists like oxycodone. Nalfurafine is a KOP-r agonist. The current study examined how nalfurafine affected the reinforcing-effect of oxycodone in adolescent male and female mice using intravenous self-administration (SA) and conditioned place preference (CPP) paradigms. Adolescent mice (5 week-old) first received surgery for catheter implantation. After recovery, mice were then placed into the SA chambers and allowed to self-administer oxycodone, 2 h per day for 14 days. Following 14-day oxycodone SA, mice were injected with saline and a single dose of nalfurafine (10, 20, 30, 40 μg/kg, s.c.) 10 min before each oxycodone SA session for 5 consecutive days. The mice were then injected with Nor-BNI (10 mg/kg, i.p.) 24 h before oxycodone SA following injection of nalfurafine (40 μg/kg, s.c.). Separate groups of male and female adolescent mice underwent oxycodone CPP or hot plate test with or without nalfurafine pre-injection. Nalfurafine decreased oxycodone SA in a dose dependent manner. Nor-BNI blocked the effect of nalfurafine on oxycodone SA. Nalfurafine significantly attenuated the oxycodone-induced hyperlocomotor activities and CPP, but enhanced oxycodone-induced analgesia. In conclusion, nalfurafine reduced the reinforcing effects of oxycodone in male and female adolescent mice. Nalfurafine also increased oxycodone-induced antinociception.
    MeSH term(s) Age Factors ; Analgesics, Opioid/administration & dosage ; Animals ; Behavior, Addictive/metabolism ; Behavior, Addictive/prevention & control ; Behavior, Addictive/psychology ; Conditioning, Psychological/drug effects ; Conditioning, Psychological/physiology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Morphinans/administration & dosage ; Oxycodone/administration & dosage ; Receptors, Opioid, kappa/agonists ; Receptors, Opioid, kappa/metabolism ; Reinforcement, Psychology ; Self Administration ; Spiro Compounds/administration & dosage
    Chemical Substances Analgesics, Opioid ; Morphinans ; Receptors, Opioid, kappa ; Spiro Compounds ; TRK 820 (25CC4N0P8J) ; Oxycodone (CD35PMG570)
    Language English
    Publishing date 2020-07-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2020.108244
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  8. Article ; Online: Kappa Opioid Receptors and Mu Opioid Receptors as Combined Targets for Medication Development for Alcoholism.

    Zhou, Yan / Kreek, Mary Jeanne

    Biological psychiatry

    2019  Volume 86, Issue 11, Page(s) 809–810

    MeSH term(s) Alcoholism ; Craving ; Drug Development ; Humans ; Naltrexone ; Receptors, Opioid, kappa ; Receptors, Opioid, mu
    Chemical Substances Receptors, Opioid, kappa ; Receptors, Opioid, mu ; Naltrexone (5S6W795CQM)
    Language English
    Publishing date 2019-10-18
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2019.08.011
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  9. Article ; Online: Clinically utilized kappa-opioid receptor agonist nalfurafine combined with low-dose naltrexone prevents alcohol relapse-like drinking in male and female mice.

    Zhou, Yan / Kreek, Mary Jeanne

    Brain research

    2019  Volume 1724, Page(s) 146410

    Abstract: Alcohol relapse is a treatment goal for alcohol dependence and the target for medications' development. Clinically utilized nalfurafine (NFF) is a potent and selective kappa- opioid receptor (KOP-r) agonist, with fewer side effects (e.g., sedation or ... ...

    Abstract Alcohol relapse is a treatment goal for alcohol dependence and the target for medications' development. Clinically utilized nalfurafine (NFF) is a potent and selective kappa- opioid receptor (KOP-r) agonist, with fewer side effects (e.g., sedation or anhedonia) than classic KOP-r full agonists. We have recently found that NFF reduces excessive alcohol drinking in mice via a KOP-r-mediated mechanism. Here, we further investigated whether NFF alone (1-10 μg/kg) or in combination with naltrexone (NTX, mu-opioid receptor [MOP-r] antagonist) altered alcohol relapse-like drinking using a mouse alcohol deprivation effect (ADE) paradigm to mimic the relapse episodes in human alcoholics. Nalmefene (NMF, clinically utilized KOP-r partial agonist with MOP-r antagonism) was used as a reference compound for the effects on mouse ADE of new NFF + NTX combination. After exposed to 3-week intermittent- access alcohol drinking (two-bottle choice, 24-h access every other day), both male and female mice displayed excessive alcohol intake and then pronounced ADE after 1-week abstinence. NFF prevented the ADE in a dose-dependent manner in both male and female mice. A combination of NFF with NTX reduced the ADE without sex differences at doses lower than those individual effective ones, suggesting synergistic effects between the two compounds. NMF prevented the ADE in both sexes, while selective KOP-r antagonist nor-BNI had no effect. Our new study suggests that a combination of clinically-utilized, potent KOP-r agonist NFF with low-dose NTX has therapeutic potential in alcohol "relapse" treatment.
    MeSH term(s) Alcohol Drinking/drug therapy ; Alcoholism/drug therapy ; Analgesics, Opioid/pharmacology ; Animals ; Drinking/drug effects ; Ethanol/pharmacology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Morphinans/metabolism ; Morphinans/pharmacology ; Naltrexone/metabolism ; Naltrexone/pharmacology ; Narcotic Antagonists/pharmacology ; Receptors, Opioid, kappa/agonists ; Receptors, Opioid, mu/metabolism ; Recurrence ; Secondary Prevention/methods ; Spiro Compounds/metabolism ; Spiro Compounds/pharmacology
    Chemical Substances Analgesics, Opioid ; Morphinans ; Narcotic Antagonists ; Receptors, Opioid, kappa ; Receptors, Opioid, mu ; Spiro Compounds ; TRK 820 (25CC4N0P8J) ; Ethanol (3K9958V90M) ; Naltrexone (5S6W795CQM)
    Language English
    Publishing date 2019-08-27
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2019.146410
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  10. Article ; Online: Combination of Clinically Utilized Kappa-Opioid Receptor Agonist Nalfurafine With Low-Dose Naltrexone Reduces Excessive Alcohol Drinking in Male and Female Mice.

    Zhou, Yan / Kreek, Mary Jeanne

    Alcoholism, clinical and experimental research

    2019  Volume 43, Issue 6, Page(s) 1077–1090

    Abstract: Background: Nalfurafine is the first clinically approved kappa-opioid receptor (KOP-r) agonist as an antipruritus drug with few side effects in humans (e.g., sedation, depression, and dysphoria). No study, however, has been done using nalfurafine on ... ...

    Abstract Background: Nalfurafine is the first clinically approved kappa-opioid receptor (KOP-r) agonist as an antipruritus drug with few side effects in humans (e.g., sedation, depression, and dysphoria). No study, however, has been done using nalfurafine on alcohol drinking in rodents or humans.
    Methods: We investigated whether nalfurafine alone or in combination with mu-opioid receptor (MOP-r) antagonist naltrexone changed excessive alcohol drinking in male and female C57BL/6J (B6) mice subjected to a chronic intermittent-access drinking paradigm (2-bottle choice, 24-hour access every other day) for 3 weeks. Neuronal proopiomelanocortin enhancer (nPE) knockout mice with brain-specific deficiency of beta-endorphin (endogenous ligand of MOP-r) were used as a genetic control for the naltrexone effects.
    Results: Single administration of nalfurafine decreased alcohol intake and preference in both male and female B6 mice in a dose-dependent manner. Pretreatment with nor-BNI (a selective KOP-r antagonist) blocked the nalfurafine effect on alcohol drinking, indicating a KOP-r-mediated mechanism. Pharmacological effects of a 5-dosing nalfurafine regimen were further evaluated: The repeated nalfurafine administrations decreased alcohol consumption without showing any blunted effects, suggesting nalfurafine did not develop a tolerance after the multidosing regimen tested. Nalfurafine did not produce any sedation (spontaneous locomotor activity), anhedonia-like (sucrose preference test), anxiety-like (elevated plus maze test), or dysphoria-like (conditioned place aversion test) behaviors, suggesting that nalfurafine had few side effects. Investigating synergistic effects between low-dose naltrexone and nalfurafine, we found that single combinations of nalfurafine and naltrexone, at doses lower than individual effective dose, profoundly decreased excessive alcohol intake in both sexes. The effect of nalfurafine on decreasing alcohol consumption was confirmed in nPE-/- mice, suggesting independent mechanisms by which nalfurafine and naltrexone reduced alcohol drinking.
    Conclusion: The clinically utilized KOP-r agonist nalfurafine in combination with low-dose naltrexone has potential in alcoholism treatment.
    MeSH term(s) Alcohol Deterrents/administration & dosage ; Alcohol Drinking/drug therapy ; Alcohol-Related Disorders/drug therapy ; Animals ; Drug Evaluation, Preclinical ; Drug Tolerance ; Female ; Male ; Mice, Inbred C57BL ; Morphinans/pharmacology ; Morphinans/therapeutic use ; Naltrexone/administration & dosage ; Naltrexone/analogs & derivatives ; Receptors, Opioid, kappa/agonists ; Saccharin/administration & dosage ; Spiro Compounds/pharmacology ; Spiro Compounds/therapeutic use ; Sucrose/administration & dosage
    Chemical Substances Alcohol Deterrents ; Morphinans ; Receptors, Opioid, kappa ; Spiro Compounds ; TRK 820 (25CC4N0P8J) ; norbinaltorphimine (36OOQ86QM1) ; Sucrose (57-50-1) ; Naltrexone (5S6W795CQM) ; Saccharin (FST467XS7D)
    Language English
    Publishing date 2019-05-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 428999-7
    ISSN 1530-0277 ; 0145-6008
    ISSN (online) 1530-0277
    ISSN 0145-6008
    DOI 10.1111/acer.14033
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