Science.gov

Sample records for morphine-induced reward caused

  1. Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

    PubMed Central

    Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

    2008-01-01

    Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

  2. Direct evidence for the involvement of the mesolimbic kappa-opioid system in the morphine-induced rewarding effect under an inflammatory pain-like state.

    PubMed

    Narita, Minoru; Kishimoto, Yayoi; Ise, Yuya; Yajima, Yoshinori; Misawa, Kaoru; Suzuki, Tsutomu

    2005-01-01

    Recent clinical studies have demonstrated that when morphine is used to control pain in cancer patients, psychological dependence is not a major concern. The present study was undertaken to ascertain the modulation of psychological dependence on morphine under a chronic pain-like state in rats. The prototypical mu-opioid receptor agonist morphine (8 mg/kg, i.p.) induced a dose-dependent place preference. In the present study, we found that an inflammatory pain-like state following formalin injection significantly suppressed the morphine-induced rewarding effect. This effect was almost reversed by s.c. pretreatment with the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI, 5 mg/kg). Furthermore, the morphine-induced increase in dopamine (DA) turnover in the limbic forebrain was significantly inhibited by treatment with formalin. This inhibition was also suppressed by pretreatment with nor-BNI. In addition, in vivo microdialysis studies clearly showed that the morphine-induced increase in the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the nucleus accumbens (N.Acc.) was significantly decreased in rats that had been pretreated with formalin. This effect was in turn reversed by the microinjection of a specific dynorphin A antibody into the N.Acc. These findings suggest that the inflammatory pain-like state induced by formalin injection may have caused a sustained activation of the kappa-opioidergic system within the N.Acc., resulting in suppression of the morphine-induced rewarding effect in rats. The present study provides further evidence of the clinical usefulness of morphine in patients suffering from severe pain. PMID:15257306

  3. Morphine-induced antinociception and reward in "humanized" mice expressing the mu opioid receptor A118G polymorphism.

    PubMed

    Henderson-Redmond, Angela N; Yuill, Matthew B; Lowe, Tammy E; Kline, Aaron M; Zee, Michael L; Guindon, Josée; Morgan, Daniel J

    2016-05-01

    The rewarding and antinociceptive effects of opioids are mediated through the mu-opioid receptor. The A118G single nucleotide polymorphism in this receptor has been implicated in drug addiction and differences in pain response. Clinical and preclinical studies have found that the G allele is associated with increased heroin reward and self-administration, elevated post-operative pain, and reduced analgesic responsiveness to opioids. Male and female mice homozygous for the "humanized" 118AA or 118GG alleles were evaluated to test the hypothesis that 118GG mice are less sensitive to the rewarding and antinociceptive effects of morphine. We found that 118AA and 118GG mice of both genders developed conditioned place preference for morphine. All mice developed tolerance to the antinociceptive and hypothermic effects of morphine. However, morphine tolerance was not different between AA and GG mice. We also examined sensitivity to the antinociceptive and hypothermic effects of cumulative morphine doses. We found that 118GG mice show reduced hypothermic and antinociceptive responses on the hotplate for 10mg/kg morphine. Finally, we examined basal pain response and morphine-induced antinociception in the formalin test for inflammatory pain. We found no gender or genotype differences in either basal pain response or morphine-induced antinociception in the formalin test. Our data suggests that homozygous expression of the GG allele in mice blunts morphine-induced hypothermia and hotplate antinociception but does not alter morphine CPP, morphine tolerance, or basal inflammatory pain response. PMID:26521067

  4. Drug-seeking behavior in an invertebrate system: evidence of morphine-induced reward, extinction and reinstatement in crayfish

    PubMed Central

    Nathaniel, Thomas I.; Panksepp, Jules; Huber, Robert

    2009-01-01

    Several lines of evidence suggest that exploring the neurochemical basis of reward in invertebrate species may provide clues for the fundamental behavioral and neurobiology underpinnings of drug addiction. How the presence of drug-sensitive reward relates to a decrease in drug-seeking behavior and reinstatement of drug seeking behavior in invertebrate systems is not known. The present study of a conditioned place preference (CPP) paradigm in crayfish (Orconectes rusticus) explores morphine-induced reward, extinction and reinstatement. Repeated intra-circulatory infusions of 2.5μg/g, 5.0μg/g and 10.0μg/g doses of morphine over 5 days serve as a reward when paired with a distinct visual or tactile environment. Morphine-induced CPP was extinguished after repeated saline injections for 5 days in the previously morphine-paired compartment. After the previously established CPP had been eliminated during the extinction phase, morphine-experienced crayfish were challenged with 2.5 μg/g, 5.0 μg/g and 10.0 μg/g respectively. The priming injections of morphine reinstated CPP in all training doses, suggesting that morphine-induced CPP is unrelenting, and that with time, it can be reinstated by morphine following extinction in an invertebrate model just like in mammals. Together with other recent studies, this work demonstrates the advantage of using crayfish as an invertebrate animal model to investigate the basic biological processes that underline exposure to mammalian drugs of abuse. PMID:18822319

  5. Morphine-induced apoptosis in the ventral tegmental area and hippocampus after the development but not extinction of reward-related behaviors in rats.

    PubMed

    Razavi, Yasaman; Alamdary, Shabnam Zeighamy; Katebi, Seyedeh-Najmeh; Khodagholi, Fariba; Haghparast, Abbas

    2014-03-01

    Some data suggest that morphine induces apoptosis in neurons, while other evidences show that morphine could have protective effects against cell death. In this study, we suggested that there is a parallel role of morphine in reward circuitry and apoptosis processing. Therefore, we investigated the effect of morphine on modifications of apoptotic factors in the ventral tegmental area (VTA) and hippocampus (HPC) which are involved in the reward circuitry after the acquisition and extinction periods of conditioned place preference (CPP). In behavioral experiments, different doses of morphine (0.5, 5, and 10 mg/kg) and saline were examined in the CPP paradigm. Conditioning score and locomotor activity were recorded by Ethovision software after acquisition on the post-conditioning day, and days 4 and 8 of extinction periods. In order to investigate the molecular mechanisms in each group, we then dissected the brains and measured the expression of apoptotic factors in the VTA and HPC by western blotting analysis. All of the morphine-treated groups showed an increase of apoptotic factors in these regions during acquisition but not in extinction period. In the HPC, morphine significantly increased the ratio of Bax/Bcl-2, caspases-3, and PARP by the lowest dose (0.5 mg/kg), but, in the VTA, a considerable increase was seen in the dose of 5 mg/kg; promotion of apoptotic factors in the HPC and VTA insinuates that morphine can affect the molecular mechanisms that interfere with apoptosis through different receptors. Our findings suggest that a specific opioid receptor involves in modification of apoptotic factors expression in these areas. It seems that the reduction of cell death in response to high dose of morphine in the VTA and HPC may be due to activation of low affinity opioid receptors which are involved in neuroprotective features of morphine. PMID:24281942

  6. Microinjection of histone deacetylase inhibitor into the ventrolateral orbital cortex potentiates morphine induced behavioral sensitization.

    PubMed

    Wei, Lai; Zhu, Yuan-Mei; Zhang, Yu-Xiang; Liang, Feng; Barry, Devin M; Gao, Hong-Yu; Li, Tao; Huo, Fu-Quan; Yan, Chun-Xia

    2016-09-01

    Accumulating evidence indicates that epigenetic regulation, such as changes in histone modification in reward-related brain regions, contributes to the memory formation of addiction to opiates and psychostimulants. Our recent results suggested that the ventrolateral orbital cortex (VLO) is involved in the memories of stress and drug addiction. Since addiction and stress memories share some common pathways, the present study was designed to investigate the role of histone deacetylase (HDAC) activity in the VLO during morphine induced-behavioral sensitization. Rats received a single exposure to morphine for establishing the behavioral sensitization model. The effect of HDAC activity in the VLO in morphine induced-behavioral sensitization was examined by microinjection of HDAC inhibitor Trichostatin A (TSA). Furthermore, the protein expression levels of extracellular signal-regulated kinase (ERK) and phosphorylated ERK (p-ERK), histone H3 lysine 9 acetylation (aceH3K9) and brain-derived neurotrophic factor (BDNF) in the VLO in morphine-induced behavioral sensitization were examined. The results showed that the bilateral VLO lesions suppressed the expression phase, but not the developmental phase of morphine-induced behavioral sensitization. Microinjection of TSA into the VLO significantly increased both the development and expression phases. Moreover, the protein levels of p-ERK, aceH3K9 and BDNF except ERK in the VLO were significantly upregulated in morphine-treated rats in the expression phase. These effects were further strengthened by intra-VLO injection of TSA. Our findings suggest that HDAC activity in the VLO could potentiate morphine-induced behavioral sensitization. The upregulated expression of p-ERK, aceH3K9 and BDNF in the VLO might be the underlying mechanism of histone acetylation enhancing the morphine-induced behavioral sensitization. PMID:27312092

  7. Morphine-induced suppression of conditioned stimulus intake: Effects of stimulus type and insular cortex lesions

    PubMed Central

    Lin, Jian-You; Roman, Christopher; Reilly, Steve

    2009-01-01

    Intake of an unconditionally preferred taste stimulus (e.g., saccharin) is reduced by contingent administration of a drug of abuse (e.g., morphine). We examined the influence of insular cortex (IC) lesions on morphine-induced suppression of an olfactory cue and two taste stimuli with different levels of perceived innate reward value. Two major findings emerged from this study. First, morphine suppressed intake of an aqueous odor as well as each taste stimulus in neurologically intact rats. Second, IC lesions disrupted morphine-induced suppression of the taste stimuli but not the aqueous odor cue. These results indicate that the perceived innate reward value of the CS is not a factor that governs drug-induced intake suppression. PMID:19631620

  8. Effects of berberine on acquisition and reinstatement of morphine-induced conditioned place preference in mice

    PubMed Central

    Vahdati Hassani, Faezeh; Hashemzaei, Mahmoud; Akbari, Edris; Imenshahidi, Mohsen; Hosseinzadeh, Hossein

    2016-01-01

    Objective: It has been shown that berberine, a major component of Berberis vulgaris extract, modulates the activity of several neurotransmitter systems including dopamine (Da) and N-methyl-D-aspartate (NMDA) contributing to rewarding and reinforcing effects of morphine. Drug craving and relapsing even after a long time of abstinence therapy are the most important problems of addiction. In the present study, we investigated the alleviating effects of berberine on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in mice. Materials and Methods: In male NMRI mice, the acquisition of CPP was established by 40 mg/kg of morphine sulphate injection and extinguished after the extinction training and reinstated by a 10 mg/kg injection of morphine. The effects of different doses of berberine (5, 10, and 20 mg/kg) on the acquisition and reinstatement induced by morphine were evaluated in a conditioned place preference test. Results: The results showed that intraperitoneal administration of berberine (5, 10, and 20 mg/kg) did not induce conditioned appetitive or aversive effects. Injection of berberine (10 and 20 mg/kg) 2 h before the morphine administration reduced acquisition of morphine-induced CPP. In addition, same doses of berberine significantly prevented the reinstatement of morphine-induced CPP. Conclusion: These results suggest that berberine can reduce the acquisition and reinstatement of morphine-induced conditioned place preference and may be useful in treatment of morphine addiction. PMID:27222833

  9. Muscarinic control of rostromedial tegmental nucleus GABA neurons and morphine-induced locomotion.

    PubMed

    Wasserman, David I; Tan, Joel M J; Kim, Jun Chul; Yeomans, John S

    2016-07-01

    Opioids induce rewarding and locomotor effects by inhibiting rostromedial tegmental GABA neurons that express μ-opioid and nociceptin receptors. These GABA neurons then strongly inhibit dopamine neurons. Opioid-induced reward, locomotion and dopamine release also depend on pedunculopontine and laterodorsal tegmental cholinergic and glutamate neurons, many of which project to and activate ventral tegmental area dopamine neurons. Here we show that laterodorsal tegmental and pedunculopontine cholinergic neurons project to both rostromedial tegmental nucleus and ventral tegmental area, and that M4 muscarinic receptors are co-localized with μ-opioid receptors associated with rostromedial tegmental GABA neurons. To inhibit or excite rostromedial tegmental GABA neurons, we utilized adeno-associated viral vectors and DREADDs to express designed muscarinic receptors (M4D or M3D respectively) in GAD2::Cre mice. In M4D-expressing mice, clozapine-N-oxide increased morphine-induced, but not vehicle-induced, locomotion. In M3D-expressing mice, clozapine-N-oxide blocked morphine-induced, but not vehicle-induced, locomotion. We propose that cholinergic inhibition of rostromedial tegmental GABA neurons via M4 muscarinic receptors facilitates opioid inhibition of the same neurons. This model explains how mesopontine cholinergic systems and muscarinic receptors in the rostromedial tegmental nucleus and ventral tegmental area are important for dopamine-dependent and dopamine-independent opioid-induced rewards and locomotion. PMID:26990801

  10. Abatement of morphine-induced slowing in gastrointestinal transit by Dai-kenchu-to, a traditional Japanese herbal medicine.

    PubMed

    Nakamura, Tomonori; Sakai, Akiko; Isogami, Issei; Noda, Kazuhiro; Ueno, Koichi; Yano, Shingo

    2002-02-01

    As a way of alleviating severe constipation in cancer patients taking morphine to relieve pain, effects of Dai-kenchu-to (DKT), a traditional Japanese herbal medicine (Kampo medicine), on gastrointestinal transit in mice or on the isolated guinea pig ileum were studied in special reference to morphine. Without altering the anti-nociceptive effect of morphine, DKT was significantly effective against morphine-induced disorder of gastrointestinal transit in mice as assessed by the charcoal meal test for the intestine and measurement of transit time for the colon tract. The results of in vitro studies with guinea pig ileum suggest that abatement of morphine-induced disorder of transit by DKT is caused by both moderate contraction of morphine-treated longitudinal muscle and relaxation of morphine-induced tonic contraction of circular muscle. PMID:11928724

  11. Severe dopaminergic neuron loss in rhesus monkey brain impairs morphine-induced conditioned place preference

    PubMed Central

    Yan, Ting; Rizak, Joshua Dominic; Wang, Jianhong; Yang, Shangchuan; Ma, Yuanye; Hu, Xintian

    2015-01-01

    It is well known that dopamine (DA) is critical for reward, but the precise role of DA in reward remains uncertain. The aim of this study was to determine what percentage of dopaminergic neurons in the primate brain is required for the expression of conditioned reward by measuring the performance of DA-deficient rhesus monkeys in a morphine-induced conditioned place preference (CPP) paradigm. Animals with mild Parkinsonian symptoms successfully developed and retained a morphine preference that was equivalent to control monkeys. However, these monkeys could not maintain the preference as well as controls when they retained severe Parkinsonian symptoms. On the other hand, monkeys initially in a severe Parkinsonian state developed a preference for morphine, but this preference was weaker than that of the controls. Histological results showed that the loss of dopaminergic neurons in monkeys that had severe Parkinsonian symptoms was about 80% in comparison to the control monkeys. All these data suggest that a severely impaired DA system alters rewarding-seeking behavior in non-human primates. PMID:26528155

  12. A ghrelin receptor (GHS-R1A) antagonist attenuates the rewarding properties of morphine and increases opioid peptide levels in reward areas in mice.

    PubMed

    Engel, Jörgen A; Nylander, Ingrid; Jerlhag, Elisabet

    2015-12-01

    Gut-brain hormones such as ghrelin have recently been suggested to have a role in reward regulation. Ghrelin was traditionally known to regulate food intake and body weight homoeostasis. In addition, recent work has pin-pointed that this peptide has a novel role in drug-induced reward, including morphine-induced increase in the extracellular levels of accumbal dopamine in rats. Herein the effect of the ghrelin receptor (GHS-R1A) antagonist, JMV2959, on morphine-induced activation of the mesolimbic dopamine system was investigated in mice. In addition, the effects of JMV2959 administration on opioid peptide levels in reward related areas were investigated. In the present series of experiment we showed that peripheral JMV2959 administration, at a dose with no effect per se, attenuates the ability of morphine to cause locomotor stimulation, increase the extracellular levels of accumbal dopamine and to condition a place preference in mice. JMV2959 administration significantly increased tissue levels of Met-enkephalin-Arg(6)Phe(7) in the ventral tegmental area, dynorphin B in hippocampus and Leu-enkephalin-Arg(6) in striatum. We therefore hypothesise that JMV2959 prevents morphine-induced reward via stimulation of delta receptor active peptides in striatum and ventral tegmental areas. In addition, hippocampal peptides that activate kappa receptor may be involved in JMV2959׳s ability to regulate memory formation of reward. Given that development of drug addiction depends, at least in part, of the effects of addictive drugs on the mesolimbic dopamine system the present data suggest that GHS-R1A antagonists deserve to be elucidated as novel treatment strategies of opioid addiction. PMID:26508707

  13. Rewards.

    PubMed

    Gunderman, Richard B; Kamer, Aaron P

    2011-05-01

    For much of the 20th century, psychologists and economists operated on the assumption that work is devoid of intrinsic rewards, and the only way to get people to work harder is through the use of rewards and punishments. This so-called carrot-and-stick model of workplace motivation, when applied to medical practice, emphasizes the use of financial incentives and disincentives to manipulate behavior. More recently, however, it has become apparent that, particularly when applied to certain kinds of work, such approaches can be ineffective or even frankly counterproductive. Instead of focusing on extrinsic rewards such as compensation, organizations and their leaders need to devote more attention to the intrinsic rewards of work itself. This article reviews this new understanding of rewards and traces out its practical implications for radiology today. PMID:21531311

  14. Inhibition of actin polymerization in the NAc shell inhibits morphine-induced CPP by disrupting its reconsolidation

    PubMed Central

    Li, Gongying; Wang, Yanmei; Yan, Min; Xu, Yunshuai; Song, Xiuli; Li, Qingqing; Zhang, Jinxiang; Ma, Hongxia; Wu, Yili

    2015-01-01

    Drug-associated contextual cues contribute to drug craving and relapse after abstinence, which is a major challenge to drug addiction treatment. Previous studies showed that disrupting memory reconsolidation impairs drug reward memory. However, the underlying mechanisms remain elusive. Although actin polymerization is involved in memory formation, its role in the reconsolidation of drug reward memory is unknown. In addition, the specific brain areas responsible for drug memory have not been fully identified. In the present study, we found that inhibiting actin polymerization in the nucleus accumbens (NAc) shell, but not the NAc core, abolishes morphine-induced conditioned place preference (CPP) by disrupting its reconsolidation in rats. Moreover, this effect persists for more than 2 weeks by a single injection of the actin polymerization inhibitor, which is not reversed by a morphine-priming injection. Furthermore, the application of actin polymerization inhibitor outside the reconsolidation window has no effect on morphine-associated contextual memory. Taken together, our findings first demonstrate that inhibiting actin polymerization erases morphine-induced CPP by disrupting its reconsolidation. Our study suggests that inhibition of actin polymerization during drug memory reconsolidation may be a potential approach to prevent drug relapse. PMID:26538334

  15. Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons

    PubMed Central

    Mazei-Robison, M.S.; Koo, J.W.; Friedman, A.; Lansink, C.S.; Robison, A.J.; Vinish, M.; Krishnan, V.; Kim, S.; Siuta, M.A.; Galli, M. A.; Niswender, K.D.; Appasani, R.; Horvath, M.C.; Neve, R.L.; Worley, P.F.; Snyder, S.H.; Hurd, Y.L.; Cheer, J.F.; Han, M.H.; Russo, S.J.; Nestler, E.J.

    2011-01-01

    SUMMARY While the abuse of opiate drugs continues to rise, the neuroadaptations that occur with long-term drug exposure remain poorly understood. We describe here a series of chronic morphine-induced adaptations in ventral tegmental area (VTA) dopamine neurons, which are mediated via downregulation of AKT-mTORC2 (mammalian target of rapamycin complex-2). Chronic opiates decrease the size of VTA dopamine neurons in rodents, an effect seen in humans as well, and concomitantly increase the excitability of the cells but decrease dopamine output to target regions. Chronic morphine decreases mTORC2 activity, and overexpression of Rictor, a component of mTORC2, prevents morphine-induced changes in cell morphology and activity. Further, local knock-out of Rictor in VTA decreases DA soma size and reduces rewarding responses to morphine, consistent with the hypothesis that these adaptations represent a mechanism of reward tolerance. Together, these findings demonstrate a novel role for AKT-mTORC2 signaling in mediating neuroadaptations to opiate drugs of abuse. PMID:22196333

  16. Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats.

    PubMed

    Wallisch, Michael; El Rody, Nehad M; Huang, Baohua; Koop, Dennis R; Baker, James R; Olsen, George D

    2012-01-15

    Respiratory depression is the main obstacle for the safe administration of morphine for acute pain after injury. Due to this complication, new delivery methods are needed to insure that safe and effective doses of opioid analgesics are administered during emergencies. A depot formulation containing a naloxone pro-drug was designed to release the antidote when morphine causes dangerous hypoxic conditions in the blood. The aim of this work was to test the naloxone release in vivo in response to a severe overdose of morphine in the Sprague-Dawley rat model. Non-invasive two-chamber plethysmography was used to monitor and record respiration and to test the capability of the naloxone pro-drug to respond to and rescue morphine-induced respiratory depression in the animal. We show that the pro-drug formulation can both prevent and reverse severe morphine induced respiratory depression. The animal model demonstrates that co-administration of the naloxone pro-drug reliably antagonizes profound respiratory depressive effects of morphine. PMID:22027217

  17. Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

    PubMed

    Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

    2014-09-01

    Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. PMID:24930812

  18. Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.

    PubMed

    Gawel, Kinga; Labuz, Krzysztof; Jenda, Malgorzata; Silberring, Jerzy; Kotlinska, Jolanta H

    2014-07-15

    The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors. PMID:24755308

  19. Stress antagonizes morphine-induced analgesia in rats

    NASA Technical Reports Server (NTRS)

    Vernikos, J.; Shannon, L.; Heybach, J. P.

    1981-01-01

    Exposure to restraint stress resulted in antagonism of the analgesic effect of administered morphine in adult male rats. This antagonism of morphine-induced analgesia by restraint stress was not affected by adrenalectomy one day prior to testing, suggesting that stress-induced secretion of corticosteroids is not critical to this antagonism. In addition, parenteral administration of exogenous adrenocorticotropin (ACTH) mimicked the effect of stress in antagonizing morphine's analgesic efficacy. The hypothesis that ACTH is an endogenous opiate antagonist involved in modulating pain sensitivity is supported.

  20. Role of dorsal hippocampal orexin-1 receptors in associating morphine reward with contextual stimuli.

    PubMed

    Riahi, Esmail; Khodagholi, Fariba; Haghparast, Abbas

    2013-08-01

    In this study, we evaluated the role of orexin receptors in the dorsal hippocampus (dHPC) in the development of morphine-induced conditioned place preference (CPP) and modification of hippocampal c-Fos and cyclic AMP response element-binding protein (CREB) levels. Orexin-A (0.5, 5, and 50 pmol) and the orexin-1 receptor antagonist, SB334867 (10, 20, and 40 nmol), were bilaterally infused into the dHPC immediately before conditioning with morphine (0.5 or 7.5 mg/kg) using the CPP task. Western blotting was then used to measure the protein levels of c-Fos, total CREB, and phosphorylated CREB (pCREB) in the hippocampus. Orexin did not enhance the rewarding efficacy of morphine (0.5 mg/kg), but caused a reduction in hippocampal c-Fos. Successful conditioning with morphine (7.5 mg/kg) was associated with increased levels of hippocampal c-Fos and CREB, but with decreased CREB phosphorylation. Intrahippocampal administration of SB334867 before conditioning sessions disrupted the rewarding effect of morphine (7.5 mg/kg) and blocked morphine-induced increases in hippocampal CREB protein levels. The results suggest that orexin signaling within the dHPC is necessary for the development of morphine CPP. Morphine reward is related to altered levels of hippocampal c-Fos and CREB. Inhibition of morphine-induced increases in CREB levels might be the underlying mechanism for the disruption of morphine CPP. PMID:23787292

  1. Short-term plasticity as cause-effect hypothesis testing in distal reward learning.

    PubMed

    Soltoggio, Andrea

    2015-02-01

    Asynchrony, overlaps, and delays in sensory-motor signals introduce ambiguity as to which stimuli, actions, and rewards are causally related. Only the repetition of reward episodes helps distinguish true cause-effect relationships from coincidental occurrences. In the model proposed here, a novel plasticity rule employs short- and long-term changes to evaluate hypotheses on cause-effect relationships. Transient weights represent hypotheses that are consolidated in long-term memory only when they consistently predict or cause future rewards. The main objective of the model is to preserve existing network topologies when learning with ambiguous information flows. Learning is also improved by biasing the exploration of the stimulus-response space toward actions that in the past occurred before rewards. The model indicates under which conditions beliefs can be consolidated in long-term memory, it suggests a solution to the plasticity-stability dilemma, and proposes an interpretation of the role of short-term plasticity. PMID:25189158

  2. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  3. Lesions of nucleus accumbens affect morphine-induced release of ascorbic acid and GABA but not of glutamate in rats.

    PubMed

    Sun, Ji Y; Yang, Jing Y; Wang, Fang; Wang, Jian Y; Song, Wu; Su, Guang Y; Dong, Ying X; Wu, Chun F

    2011-10-01

    Our previous studies have shown that local perfusion of morphine causes an increase of extracellular ascorbic acid (AA) levels in nucleus accumbens (NAc) of freely moving rats. Lines of evidence showed that glutamatergic and GABAergic were associated with morphine-induced effects on the neurotransmission of the brain, especially on the release of AA. In the present study, the effects of morphine on the release of extracellular AA, γ-aminobutyric acid (GABA) and glutamate (Glu) in the NAc following bilateral NAc lesions induced by kainic acid (KA) were studied by using the microdialysis technique, coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD) and fluorescent detection (HPLC-FD). The results showed that local perfusion of morphine (100 µM, 1 mM) in NAc dose-dependently increased AA and GABA release, while attenuated Glu release in the NAc. Naloxone (0.4 mM) pretreated by local perfusion to the NAc, significantly blocked the effects of morphine. After NAc lesion by KA (1 µg), morphine-induced increase in AA and GABA were markedly eliminated, while decrease in Glu was not affected. The loss effect of morphine on AA and GABA release after KA lesion could be recovered by GABA agonist, musimol. These results indicate that morphine-induced AA release may be mediated at least by µ-opioid receptor. Moreover, this effect of morphine possibly depend less on the glutamatergic afferents, but more on the GABAergic circuits within this nucleus. Finally, AA release induced by local perfusion of morphine may be GABA-receptor mediated and synaptically localized in the NAc. PMID:20731632

  4. Intrathecal rapamycin attenuates morphine-induced analgesic tolerance and hyperalgesia in rats with neuropathic pain

    PubMed Central

    Xu, Ji-Tian; Sun, Linlin; Lutz, Brianna Marie; Bekker, Alex; Tao, Yuan-Xiang

    2015-01-01

    Repeated and long-term administration of opioids is often accompanied by the initiation of opioid-induced analgesic tolerance and hyperalgesia in chronic pain patients. Our previous studies showed that repeated intrathecal morphine injection activated the mammalian target of rapamycin complex 1 (mTORC1) in spinal dorsal horn neurons and that blocking this activation prevented the initiation of morphine-induced tolerance and hyperalgesia in healthy rats. However, whether spinal mTORC1 is required for morphine-induced tolerance and hyperalgesia under neuropathic pain conditions remains elusive. We here observed the effect of intrathecal infusion of rapamycin, a specific mTORC1 inhibitor, on morphine-induced tolerance and hyperalgesia in a neuropathic pain model in rats induced by the fifth lumbar spinal nerve ligation (SNL). Continuous intrathecal infusion of morphine for one week starting on day 8 post-SNL led to morphine tolerance demonstrated by morphine-induced reduction in maximal possible analgesic effect (MPAE) to tail heat stimuli and ipsilateral paw withdrawal threshold (PWT) to mechanical stimuli in SNL rats. Such reduction was attenuated by co-infusion of rapamycin. Co-infusion of rapamycin also blocked morphine tolerance demonstrated by attenuation of morphine-induced reduction in MPAE in sham rats and morphine-induced hyperalgesia demonstrated by the reverse of morphine-induced reduction in PWT on both sides of sham rats and on the contralateral side of SNL rats. The results suggest that mTORC1 inhibitors could serve as promising medications for use as adjuvants with opioids in clinical neuropathic pain management. PMID:26339682

  5. Effects of Estrogen Receptor Modulators on Morphine Induced Sensitization in Mice Memory

    PubMed Central

    Anoush, Mahdieh; Jani, Ali; Sahebgharani, Moosa; Jafari, Mohammad Reza

    2015-01-01

    Objective: In this study, the effects of estradiol valerate and raloxifenea selective estrogen receptor modulator; (SERM) on morphine induced sensitization were examined in mice memory, according to the step-down passive avoidance task. Method: The mice received morphine or estradiol and raloxifene for three days alone or in combination with morphine. After a drug free period of 5 days, the subjects received saline or morphine as pre- training treatments followed by a pre-test saline administration. The memory retrieval was evaluated using step-down passive avoidance test both on the training and test day. Results: The results illustrated that the three- day administration of morphine induced sensitization through the enhancement of memory retrieval (morphine induced sensitization in mice memory). Both the three- day administration of estradiol valerate alone and with morphine (5 mg/kg) restored memory. On the other hand, the three- day administration of raloxifene had no effect on memory retrieval alone, but declined morphine induced sensitization in mice memory. Conclusion: The results of the study indicated that there is an interaction between estrogen receptor modulators and morphine induced sensitization in mice memory. PMID:26877753

  6. Proteomic analysis of rat prefrontal cortex in three phases of morphine-induced conditioned place preference.

    PubMed

    Yang, Liu; Sun, Zhong Sheng; Zhu, Yong-ping

    2007-06-01

    Morphological alterations of synapse are found after morphine administration, suggesting that regulation of synaptic plasticity may be one of the mechanisms of neuroadaptation in addiction. However, the molecular basis underlying the abnormal synapse morphological and physiological changes in the morphine-induced dependence, withdraw, and relapse is not well understood. As prefrontal cortex (PFC) is one of the most important brain regions, which provides executive control over drug use and is severely impaired in many addicts, systematic analysis of the biochemical and molecular alteration of synaptic fraction of PFC in morphine-induced neuroadaptation is necessary. In this study, differential protein expression profiling of synaptic fraction of rat PFC based on morphine-induced conditioned place preference (CPP) model was performed with two-dimensional gel electrophoresis (2-DE). Our results showed that a total of 80 proteins were differentially expressed by 2-DE analysis during three phases of CPP assay. Of them, 58 were further identified by mass spectrometry. These proteins were classified into multiple categories, such as energy metabolism, signal transduction, synaptic transmission, cytoskeletal proteins, chaperones, and local synaptic protein synthetic machinery according to their biological functions. Our study provides a global view of synaptic-related molecular networking in PFC under morphine-induced dependence, withdraw, and relapse, indicative of a concerted biological process in neuroadaptation under chronic morphine exposure. PMID:17444669

  7. Proteome Analysis of Rat Hippocampus Following Morphine-induced Amnesia and State-dependent Learning

    PubMed Central

    Jafarinejad-Farsangi, Saeideh; Farazmand, Ali; Rezayof, Ameneh; Darbandi, Niloufar

    2015-01-01

    Morphine’s effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of protein expression induced by morphine, we compared rat hippocampal proteome either in morphine-induced amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of morphine decreased step-through latency. Pre-test administration of morphine induced state-dependent retrieval of the memory acquired under post-training morphine influence. In the hippocampus, a total of 18 proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal proteins altered in morphine-induced amnesia and ten proteins were found to change in the hippocampus of animals that had received post-training and pre-test morphine. These proteins show known functions in cytoskeletal architecture, cell metabolism, neurotransmitter secretion and neuroprotection. The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level. In addition, our proteomicscreensuggests that morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity. PMID:25901168

  8. Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: conditioned place preference to morphine induces CREB phosphorylation.

    PubMed

    Morón, José A; Gullapalli, Srinivas; Taylor, Chirisse; Gupta, Achla; Gomes, Ivone; Devi, Lakshmi A

    2010-03-01

    Opiate addiction is a chronic, relapsing behavioral disorder where learned associations that develop between the abused opiate and the environment in which it is consumed are brought about through Pavlovian (classical) conditioning processes. However, the signaling mechanisms/pathways regulating the mechanisms that underlie the responses to opiate-associated cues or the development of sensitization as a consequence of repeated context-independent administration of opiates are unknown. In this study we examined the phosphorylation levels of various classic signaling molecules in brain regions implicated in addictive behaviors after acute and repeated morphine administration. An unbiased place conditioning protocol was used to examine changes in phosphorylation that are associated with (1) the expression of the rewarding effects of morphine and (2) the sensitization that develops to this effect. We also examined the effects of a delta-receptor antagonist on morphine-induced conditioned behavior and on the phosphorylation of classic signaling molecules in view of data showing that blockade of delta-opioid receptor (deltaOR) prevents the development of sensitization to the rewarding effects of morphine. We find that CREB phosphorylation is specifically induced upon the expression of a sensitized response to morphine-induced conditioned behavior in brain areas related to memory consolidation, such as the hippocampus and cortex. A similar effect is also observed, albeit to a lesser extent, in the case of the GluR1 subunit of AMPA glutamate receptor. These increases in the phosphorylation levels of CREB and pGluR1 are significantly blocked by pretreatment with a deltaOR antagonist. These results indicate a critical role for phospho-CREB, AMPA, and deltaOR activities in mediating the expression of a sensitized response to morphine-dependent conditioned behavior. PMID:19956087

  9. Reversal of morphine-induced respiratory depression by doxapram in anesthetized rats.

    PubMed

    Haji, Akira; Kimura, Satoko; Ohi, Yoshiaki

    2016-06-01

    The present study was undertaken to investigate whether doxapram, a blocker of tandem pore K(+) (TASK-1/-3) channels, is a useful tool for recovery from morphine-induced ventilatory disturbances. Spontaneous ventilation and the hind leg withdrawal response against noxious thermal stimulation were recorded simultaneously in anesthetized rats. Morphine (1.0mg/kg, i.v.) decreased the minute volume resulting from depression of the ventilatory rate and tracheal airflow. Concomitantly, it prolonged the latency of withdrawal response against the thermal stimulation. Subsequent intravenous injection of doxapram recovered the morphine-induced ventilatory depression. This effect of doxapram declined rapidly after a single injection (1.0-3.0mg/kg, i.v.) but persisted with a continuous infusion (0.33mg/kg/min). Neither single injection nor continuous infusion of doxapram had any detectable effect on the analgesic potency of morphine. The central respiratory activity was recorded from the phrenic nerve in anesthetized, vagotomized, paralyzed and artificially ventilated rats. Morphine (3.0mg/kg, i.v.) induced respiratory depression, characterized by a prolonged plateau-like inspiratory discharge (apneustic discharge) in the phrenic nerve. Doxapram (10mg/kg, i.v.) restored the morphine-induced apneustic discharge to an augmenting inspiratory discharge. This study demonstrated that doxapram counteracted morphine-induced respiratory depression by stimulating the central respiratory network without compromising morphine antinociception. These results support the clinical use of doxapram for amelioration of ventilatory disturbances in patients treated with opioids. PMID:27038521

  10. Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction.

    PubMed

    Wu, XuJun; Zhao, Ning; Bai, Fan; Li, ChuanYu; Liu, CiRong; Wei, JingKuan; Zong, Wei; Yang, LiXin; Ryabinin, Andrey E; Ma, YuanYe; Wang, JianHong

    2016-05-01

    Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction

  11. The extinction of morphine-induced conditioned place preference by histone deacetylase inhibition.

    PubMed

    Wang, Ru; Zhang, Yan; Qing, Hua; Liu, Mei; Yang, Peng

    2010-10-11

    Recent evidence suggests that epigenetic mechanisms have an important role in the development of addictive behavior. However, little is known about the role of epigenetic mechanisms in the extinction of morphine-induced behavioral changes. In this study, we will examine the effect of histone deacetylase (HDAC) inhibitors on extinction of morphine-induced conditioned place preference (CPP). To facilitate extinction, rats will be administered an HDAC inhibitor (HDACi) following nonreinforced exposure to the conditioned context. To measure persistence, rats were subject to a reinstatement test using 3 mg/kg dose of morphine. To exclude the effect of repeated NaBut injections themselves on morphine-CPP in the absence of extinction session, rats received injection of either NaBut or vehicle for 8 days. We found that HDAC inhibition during nonconfined extinction or confined extinction consolidation can facilitate extinction of morphine-induced CPP. We also showed that the extinction of drug seeking via HDAC inhibition modulates extinction learning such that reinstatement behavior is significantly attenuated. There is no effect of repeated NaBut injections themselves on morphine-CPP in the absence of extinction session. In conclusion, our results extend earlier reports on the ability of HDACi to modify the behavioral effects of drugs of abuse. Our increasing understanding of these epigenetic mechanisms will provide key answers to basic processes in drug addiction and hopefully provide insight into designing improved treatments for drug addiction. PMID:20691756

  12. Bergenin decreases the morphine-induced physical dependence via antioxidative activity in mice.

    PubMed

    Yun, Jaesuk; Lee, Yeonju; Yun, Kyunghwa; Oh, Seikwan

    2015-06-01

    Oxidative stress plays a role in the development of physical dependence induced by morphine. Bergenin, a polyphenol found in many Asian, African, and South American medicinal plants, is a potent antinarcotic agent with wide spectrum of pharmacological activities including antioxidant action. In the present study, we observed that bergenin decreased the development of physical dependence induced by morphine in mice and the antioxidant activity of bergenin plays a role in the antinarcotic effects through adapting to morphine-induced oxidative stress in the brain. The naloxone-precipitated withdrawal symptom (jumping frequency) was significantly ameliorated (50% of control group) by administration of bergenin (20 mg/kg) in morphine-treated mice. Furthermore, morphine-induced down-regulation of glutathione (GSH) contents was reversed by bergenin administration in the frontal cortex and liver. Bergenin had no effects on the increased levels of nfr2-dependent antioxidant enzyme HO1 and NQO1 in the frontal cortex, striatum, and liver of morphine-treated mice. However, the morphine-induced increase in nrf2 nuclear translocation in the frontal cortex and striatum was inhibited by bergenin treatment. These results suggest that bergenin has a potential antinarcotic effect via regulation of GSH contents and oxidative stress. PMID:25542428

  13. Tolerance to morphine-induced antinociception is decreased by chronic sucrose or polycose intake.

    PubMed

    D'Anci, K E

    1999-05-01

    Chronic intake of palatable fluids alters morphine-induced antinociception. Two experiments were conducted to evaluate how long-term access to palatable fluids alters the development of tolerance to morphine-induced antinociception. In Experiment 1, 40 adult male Long-Evans rats were used. In addition to ad lib chow and water, 10 rats were given a 0.15% saccharin solution, 10 were given a 32% sucrose solution, and 10 were given a 32% Polycose solution to drink for 3 weeks. Ten rats were given chow and water alone, and served as dietary controls. Morphine-induced antinociception was assessed using the radiant-heat tail-flick method (TF). Half of the animals in each dietary condition were given preexposure to 7.5 mg/kg morphine; the other half received saline. All rats were given a TF 30-min postinjection. To determine whether tolerance developed, a cumulative dose paradigm (0.625, 1.25, 2.5, 5.0, 10.0 mg/kg) was employed 1 week after initial morphine injections, and was repeated at weekly intervals for 3 weeks. Antinociception was significantly lower in rats preexposed to morphine relative to rats preexposed to saline. Although all rats displayed decreased antinociception relative to the first morphine injection, rats that drank saccharin showed greater reductions in morphine-induced antinociception relative to rats that drank sucrose or Polycose. Experiment 2 was conducted to determine whether initial pairing of the TF with morphine preexposure produced differences in the development of opioid tolerance. All conditions and procedures were identical to Experiment 1, except that the initial morphine and saline injections were not followed by TF. As in Experiment 1, rats that drank saccharin showed less antinociception than rats that drank sucrose or Polycose. The present results suggest that long-term intake of palatable nutritive solutions curbs tolerance to morphine-induced antinociception, whereas long-term intake of a nonnutritive, sweet saccharin solution does

  14. Activation of p38 signaling in the microglia in the nucleus accumbens contributes to the acquisition and maintenance of morphine-induced conditioned place preference.

    PubMed

    Zhang, Xue-Qin; Cui, Yu; Cui, Yue; Chen, Yu; Na, Xiao-Dong; Chen, Feng-Ying; Wei, Xu-Hong; Li, Yong-Yong; Liu, Xian-Guo; Xin, Wen-Jun

    2012-02-01

    Several lines of evidence have suggested that activated glia contributes to morphine-induced reward (conditioned place preference, CPP). Compared to well-defined roles of astrocyte in morphine CPP, the role of microglia in the nucleus accumbens (NAc) remains poorly characterized. The aim of the present study was to investigate the distinct role of microglia in morphine-induced CPP. Systemic administration of morphine (7.5 mg/kg for 5 days) induced significant preference for the morphine-paired compartment in rats, which lasted for at least 6 days after cessation of morphine treatment. Immunohistochemistry results showed that activation of p38 in the NAc microglia induced by chronic morphine treatment maintained on day 11. Bilateral intra-NAc injection of minocycline, a putative microglia inhibitor, or SB203580, an inhibitor of p38, prior to morphine administration not only inhibited p38 activation in the microglia but impaired the acquisition of CPP. On the day following the acquisition of morphine CPP, a single injection of minocycline or SB203580 failed to block the expression of CPP. Notably, pretreatment with minocycline or SB203580 for 5 days following the acquisition of morphine CPP significantly suppressed the activation of p38 and attenuated the maintenance of morphine CPP. Collectively, our present study indicates that the p38 signaling in the NAc microglia may play an important role in the acquisition and maintenance but not the expression of morphine CPP, and provides new evidence that microglia might be a potential target for the therapy of morphine addiction. PMID:22004988

  15. Protective role of taurine against morphine-induced neurotoxicity in C6 cells via inhibition of oxidative stress.

    PubMed

    Zhou, Jiaqing; Li, Yan; Yan, Guangyan; Bu, Qian; Lv, Lei; Yang, Yanzhu; Zhao, Jinxuan; Shao, Xue; Deng, Yi; Zhu, Ruimin; Zhao, Yinglan; Cen, Xiaobo

    2011-11-01

    This study was carried out to investigate the protective role of taurine (2-aminoethanesulphonicacid) against morphine-induced neurotoxicity in C6 cells. It was found that taurine significantly increased the viability of C6 cells treated by morphine, showing the neuroprotective role against morphine-induced neurotoxicity. However, such neuroprotective effect of taurine could not be blocked by bicuculline, an antagonist of gamma-amino butyrate (GABA) receptor. To determine the oxidative damage induced by morphine, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured in C6 cells. The decreased activities of SOD, CAT, and GPx in C6 cells were observed after morphine treatment for 48 h. However, taurine administration effectively ameliorated morphine-induced oxidative insult. To estimate anti-apoptosis effect of taurine, flow cytometry analysis as well as detection for caspase-3 and Bcl-2 expressions was performed after morphine exposure for 48 h. It was found that Bcl-2 expression was down regulated by morphine, whereas taurine could reverse morphine-induced decrease in Bcl-2 expression. Taurine showed no effect on caspase-3 expression. Collectively, the results show that taurine possesses the capability to ameliorate morphine-induced oxidative insult and apoptosis in C6 cells, probably due to its antioxidant activity rather than activation of GABA receptors. PMID:21611853

  16. Inhibitory effects of forced swim stress and corticosterone on the acquisition but not expression of morphine-induced conditioned place preference: involvement of glucocorticoid receptor in the basolateral amygdala.

    PubMed

    Attarzadeh-Yazdi, Ghassem; Karimi, Sara; Azizi, Pegah; Yazdi-Ravandi, Saeid; Hesam, Soghra; Haghparast, Abbas

    2013-09-01

    Addiction is a common chronic psychiatric disease which represents a global problem and stress has an important role to increase drug addiction and relapse. In the present study, we investigated the effects of physical stress and exogenous corticosterone on the acquisition and expression of morphine-induced conditioned place preference (CPP). Also, we tried to find out the role of glucocorticoid receptors (GRs) of basolateral amygdala (BLA) in this regard. In the CPP paradigm, conditioning score and locomotion activity were recorded by Ethovision software. Male adult rats received forced swim stress (FSS) as a physical stress or corticosterone (10 mg/kg; ip) as a dominant stress hormone in rodents, 10min before morphine injection (5 mg/kg; sc) during three conditioning days (acquisition) or just prior to CPP test in the post-conditioning day (expression). In FSS procedure, animals were forced to swim for 6 min in cylinder filled with water (24-27 °C). To evaluate the role of glucocorticoid receptors in the BLA, different doses of mifepristone (RU38486) as a GR antagonist were injected into the BLA (0.3, 3 and 30 ng/side) during 3-day conditioning phase before FSS or injection of corticosterone in morphine-CPP paradigm. The results showed that FSS and corticosterone reduce the acquisition but not expression of morphine-induced CPP. Moreover, blockade of GRs in the BLA could diminish the inhibitory effects of FSS or corticosterone on the acquisition of morphine-induced CPP. It seems that stress exerts its effect on reward pathway via glucocorticoid receptors in the BLA. PMID:23800381

  17. Role of C-fibers in pain and morphine induced analgesia/hyperalgesia in rats

    PubMed Central

    Alizadeh, Zahra; Behnam-Rassouli, Morteza; Hosseini, Shirin

    2014-01-01

    Background Usual dosage of morphine (10 mg/kg) induces analgesia and ultra-low dose (ULD) of morphine (1 µg/kg); hyperalgesia, and C-fibers are also bearing µ-opioid receptors; here the importance of C-fibers on pain and morphine induced analgesia/hyperalgesia is questioned and investigated using pain evaluation methods and infant capsaicin treating for C-fibers lesioning. Methods Wistar male rats (200-250 grams) were assigned to three categories i.e. control, sham (receiving neonatal capsaicin vehicle) and c-lesion (receiving neonatal capsaicin), each one with three groups (n=7). They were injected intraperitoneally with single dosage of saline, 10 mg/kg or 1 µg/kg morphine, respectively. Thermal pain threshold was evaluated using the tail flick test before and 30 minutes after the injections. Chemical pain was assessed using the formalin test (FT) 30 minutes after the administrations. Results Results indicated that thermal (P < 0.001) and chemical pains in both neurogenic and inflammatory phases of FT (P < 0.05) were reduced in C-lesion animals. In the C-normal and C-lesion animals, 10 mg/kg morphine exerted analgesia both in thermal (P < 0.001) and two phases of FT (P < 0.01), but it was more potent in C-lesion animals (P < 0.05). Although ULD of morphine in C-normal animals produced hyperalgesic effect in thermal and chemical pains (P < 0.001), in C-lesion animals, it produced analgesia (P < 0.05) at the neurogenic phase of FT. Conclusion Results can raise the C-fibers involvement for a significant portion of nociceptive transmission, because C-lesioning potentiated morphine induced analgesia and eliminated ULD of morphine induced hyperalgesia. Therefore C and Aδ fibers can be involved in morphine analgesia; while, just C-fibers are possibly responsible for only presynaptically hyperalgesic/excitatory action of ULD in morphine. PMID:24800043

  18. [Morphine-induced Anaphylaxis before Induction of Anesthesia].

    PubMed

    Takahashi, Kei; Suzuki, Hiroaki; Arai, Takero; Okuda, Yasuhisa

    2016-04-01

    We describe a case of anaphylaxia that occurred in a 67-year-old man. He was planned to have an operation on mitral valve prolapse (MVP) for mitral regurgitation (MR). Morphine 5 mg was injected intramusculaly 45 min before operation. Since then, he felt itchy sensation around his inguinal region. After he came to the operating room, he felt itchy sensation all over the body. Initially, his vatal signs were stable. We started to give extracellular fluid including ulinastatin 300,000 U, methylprednisolone 2 g, and ranitidine 50 mg. A few minutes later, he had nettle rash all over the body and his blood pressure decreased to 40/20 mmHg, and the heart rate increased to 120 beats x min(-1). Soon after, he had pulseless electric activity (PEA). We started chest compression and tracheal intubation. We injected adrenaline 1 mg. After doing the continuous chest compression for 2 min, he revived. He had continuous medications including dopamine 5 μg x kg(-1) x min(-1), dobutamine 5 μg x kg(-1) x min(-1), noradrenaline 0.05 μg x kg(-1) x min(-1). We cancelled the operation, and he was transfered to the high care unit (HCU), where his blood pressure was 120/65 mmHg, and heart rate 120 beats x min(-1). After 24 hours, we extubated his trachea. In this case, morphine was considered to be the most likely cause for anaphylaxis. PMID:27188106

  19. Monoamine mediation of the morphine-induced activation of mice

    PubMed Central

    Carroll, Bernard J.; Sharp, Peter T.

    1972-01-01

    1. The dose-response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established. 2. The activation response can be modified by drugs which affect either catecholamines or indoleamines. 3. The monoamine precursors L-DOPA and 5-hydroxytryptophan potentiate the response. 4. The monoamine synthesis inhibitors α-methyl-p-tyrosine and p-chlorophenylalanine reduce the response. 5. Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation. 6. Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine. 7. Blockade of α-adrenoceptors with phentolamine or phenoxybenzamine reduced the response. 8. Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response. 9. The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard. 10. The tricyclic antidepressant drug imipramine potentiated the response. 11. The morphine antagonist nalorphine completely prevented the response. 12. The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response. 13. We conclude that dopamine, noradrenaline and 5-hydroxytryptamine are all involved in the normal activation response of grouped mice to morphine, with dopaminergic mechanisms being of primary importance. PMID:4263794

  20. Sex differences in morphine-induced behavioral sensitization and social behaviors in ICR mice

    PubMed Central

    ZHAN, Bo; MA, Hong-Yuan; WANG, Jian-Li; LIU, Chao-Bao

    2015-01-01

    Gender and genetic strain are two prominent variants that influence drug abuse. Although certain sex-related behavioral responses have been previously characterized in ICR mice, little is known about the effects of sex on morphine-induced behavioral responses in this outbred strain. Therefore, in this study, we investigated the sex differences of morphine-induced locomotion, anxiety-like and social behaviors in ICR mice. After morphine or saline exposure for four consecutive days (twice daily), increased locomotion, more time spent in the central area, as well as attenuated rearing and self-grooming behaviors were found in morphine-treated females in an open field; no differences were found in locomotion and the time spent in the central area between male and female controls. When interacting with the same-sex individuals, female controls were engaged in more social investigation, following, body contacting and self-grooming behaviors than controls; morphine exposure reduced contacting and self-grooming behaviors in females; in contrast, these effects were not found in males. These results indicate that female ICR mice are more prosocial and are more susceptible to morphine exposure than males. PMID:25855229

  1. Interactive HIV-1 Tat and Morphine-Induced Synaptodendritic Injury Is Triggered through Focal Disruptions in Na+ Influx, Mitochondrial Instability, and Ca2+ Overload

    PubMed Central

    Knapp, Pamela E.; Zou, Shiping; Marks, William D.; Bowers, M. Scott; Akbarali, Hamid I.; Hauser, Kurt F.

    2014-01-01

    Synaptodendritic injury is thought to underlie HIV-associated neurocognitive disorders and contributes to exaggerated inflammation and cognitive impairment seen in opioid abusers with HIV-1. To examine events triggering combined transactivator of transcription (Tat)- and morphine-induced synaptodendritic injury systematically, striatal neuron imaging studies were conducted in vitro. These studies demonstrated nearly identical pathologic increases in dendritic varicosities as seen in Tat transgenic mice in vivo. Tat caused significant focal increases in intracellular sodium ([Na+]i) and calcium ([Ca2+]i) in dendrites that were accompanied by the emergence of dendritic varicosities. These effects were largely, but not entirely, attenuated by the NMDA and AMPA receptor antagonists MK-801 and CNQX, respectively. Concurrent morphine treatment accelerated Tat-induced focal varicosities, which were accompanied by localized increases in [Ca2+]i and exaggerated instability in mitochondrial inner membrane potential. Importantly, morphine's effects were prevented by the μ-opioid receptor antagonist CTAP and were not observed in neurons cultured from μ-opioid receptor knock-out mice. Combined Tat- and morphine-induced initial losses in ion homeostasis and increases in [Ca2+]i were attenuated by the ryanodine receptor inhibitor ryanodine, as well as pyruvate. In summary, Tat induced increases in [Na+]i, mitochondrial instability, excessive Ca2+ influx through glutamatergic receptors, and swelling along dendrites. Morphine, acting via μ-opioid receptors, exacerbates these excitotoxic Tat effects at the same subcellular locations by mobilizing additional [Ca2+]i and by further disrupting [Ca2+]i homeostasis. We hypothesize that the spatiotemporal relationship of μ-opioid and aberrant AMPA/NMDA glutamate receptor signaling is critical in defining the location and degree to which opiates exacerbate the synaptodendritic injury commonly observed in neuroAIDS. PMID:25232120

  2. BK channels in microglia are required for morphine-induced hyperalgesia

    PubMed Central

    Hayashi, Yoshinori; Morinaga, Saori; Zhang, Jing; Satoh, Yasushi; Meredith, Andrea L.; Nakata, Takahiro; Wu, Zhou; Kohsaka, Shinichi; Inoue, Kazuhide; Nakanishi, Hiroshi

    2016-01-01

    Although morphine is a gold standard medication, long-term opioid use is associated with serious side effects, such as morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance. Microglia-to-neuron signalling is critically involved in pain hypersensitivity. However, molecules that control microglial cellular state under chronic morphine treatment remain unknown. Here we show that the microglia-specific subtype of Ca2+-activated K+ (BK) channel is responsible for generation of MIH and anti-nociceptive tolerance. We find that, after chronic morphine administration, an increase in arachidonic acid levels through the μ-opioid receptors leads to the sole activation of microglial BK channels in the spinal cord. Silencing BK channel auxiliary β3 subunit significantly attenuates the generation of MIH and anti-nociceptive tolerance, and increases neurotransmission after chronic morphine administration. Therefore, microglia-specific BK channels contribute to the generation of MIH and anti-nociceptive tolerance. PMID:27241733

  3. BK channels in microglia are required for morphine-induced hyperalgesia.

    PubMed

    Hayashi, Yoshinori; Morinaga, Saori; Zhang, Jing; Satoh, Yasushi; Meredith, Andrea L; Nakata, Takahiro; Wu, Zhou; Kohsaka, Shinichi; Inoue, Kazuhide; Nakanishi, Hiroshi

    2016-01-01

    Although morphine is a gold standard medication, long-term opioid use is associated with serious side effects, such as morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance. Microglia-to-neuron signalling is critically involved in pain hypersensitivity. However, molecules that control microglial cellular state under chronic morphine treatment remain unknown. Here we show that the microglia-specific subtype of Ca(2+)-activated K(+) (BK) channel is responsible for generation of MIH and anti-nociceptive tolerance. We find that, after chronic morphine administration, an increase in arachidonic acid levels through the μ-opioid receptors leads to the sole activation of microglial BK channels in the spinal cord. Silencing BK channel auxiliary β3 subunit significantly attenuates the generation of MIH and anti-nociceptive tolerance, and increases neurotransmission after chronic morphine administration. Therefore, microglia-specific BK channels contribute to the generation of MIH and anti-nociceptive tolerance. PMID:27241733

  4. Saccharin effects on morphine-induced antinociception in the mouse formalin test.

    PubMed

    Abdollahi, M; Nikfar, S; Habibi, L

    2000-09-01

    This study was performed to investigate the role of sweetness and taste sensations of the non-caloric sweetener saccharin on pain and morphine antinociception by the formalin test in mice. The formalin test was chosen because it measures the response to a long-lasting nociceptive stimulus and thus may closely resemble clinical pain. The total time (seconds) spent licking and biting the injected paw (indices of nociception) during periods of 0-5 min (early phase) and 10-30 min (late phase) were measured as an indicator of pain and inflammatory responses. A 12 days pretreatment of animals with saccharin (0.04%, 0.08%, 0.16%) produced complex effects on the action of morphine. All doses significantly potentiated the low dose (1.5 mgkg(-1)) of morphine-induced analgesia in the early phase significantly but antagonized the effect of morphine (3 mgkg(-1)). The effect of high doses of morphine (6-9 mgkg(-1)) was antagonized by the low dose of saccharin (0.04%), but the effect of morphine (6 mgkg(-1)) was potentiated with high concentrations of saccharin (0.08% and 0.16%). All doses of saccharin decreased the analgesic effect of morphine at a dose of 9 mgkg(-1). Analgesic effects of low doses of morphine (1.5-3 mgkg(-1)) were decreased by all doses of saccharin in the late phase. Different concentrations of saccharin also affected the antagonistic effect of naloxone (0.4 mgkg(-1)) on morphine-induced analgesia in both phases of the formalin test. The high dose of saccharin (0.16%) potentiated the effect of naloxone in the late phase. The results obtained suggest that sweet sensation is an important factor in mediating morphine analgesic properties. It is therefore inappropriate to use different concentrations of sweet saccharin solutions interchangeably. PMID:10945932

  5. Morphine-Induced Preconditioning: Involvement of Protein Kinase A and Mitochondrial Permeability Transition Pore

    PubMed Central

    Dorsch, Marianne; Behmenburg, Friederike; Raible, Miriam; Blase, Dominic; Grievink, Hilbert; Hollmann, Markus W.; Heinen, André; Huhn, Ragnar

    2016-01-01

    Background Morphine induces myocardial preconditioning (M-PC) via activation of mitochondrial large conductance Ca2+-sensitive potassium (mKCa) channels. An upstream regulator of mKCa channels is protein kinase A (PKA). Furthermore, mKCa channel activation regulates mitochondrial bioenergetics and thereby prevents opening of the mitochondrial permeability transition pore (mPTP). Here, we investigated in the rat heart in vivo whether 1) M-PC is mediated by activation of PKA, and 2) pharmacological opening of the mPTP abolishes the cardioprotective effect of M-PC and 3) M-PC is critically dependent on STAT3 activation, which is located upstream of mPTP within the signalling pathway. Methods Male Wistar rats were randomised to six groups (each n = 6). All animals underwent 25 minutes of regional myocardial ischemia and 120 minutes of reperfusion. Control animals (Con) were not further treated. Morphine preconditioning was initiated by intravenous administration of 0.3 mg/kg morphine (M-PC). The PKA blocker H-89 (10 μg/kg) was investigated with and without morphine (H-89+M-PC, H-89). We determined the effect of mPTP opening with atractyloside (5 mg/kg) with and without morphine (Atr+M-PC, Atr). Furthermore, the effect of morphine on PKA activity was tested in isolated adult rat cardiomyocytes. In further experiments in isolated hearts we tested the protective properties of morphine in the presence of STAT3 inhibition, and whether pharmacological prevention of the mPTP-opening by cyclosporine A (CsA) is cardioprotective in the presence of STAT3 inhibition. Results Morphine reduced infarct size from 64±5% to 39±9% (P<0.05 vs. Con). H-89 completely blocked preconditioning by morphine (64±9%; P<0.05 vs. M-PC), but H-89 itself had not effect on infarct size (61±10%; P>0.05 vs. Con). Also, atractyloside abolished infarct size reduction of morphine completely (65±9%; P<0.05 vs. M-PC) but had no influence on infarct size itself (64±5%; P>0.05 vs. Con). In isolated

  6. The α1 adrenoceptors in ventrolateral orbital cortex contribute to the expression of morphine-induced behavioral sensitization in rats.

    PubMed

    Wei, Lai; Zhu, Yuan-Mei; Zhang, Yu-Xiang; Liang, Feng; Li, Teng; Gao, Hong-Yu; Huo, Fu-Quan; Yan, Chun-Xia

    2016-01-01

    The aim of the present study was to investigate the effect of microinjection of benoxathian, selective α1 adrenoceptor antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced behavioral sensitization and its underlying molecular mechanism in rats. A single morphine treatment protocol was used in establishing the behavioral sensitization model. The effect of bilateral intra-VLO benoxathian injection on locomotor activity was examined and the protein expression levels of α1 adrenoceptors and activation of extracellular signal-regulated kinase (ERK) in the VLO were detected after locomotor test. The results showed that a single injection of morphine could induce behavioral sensitization by a low challenge dosage of morphine after a 7-days drug free period. Benoxathian significantly suppressed the expression but not the development of morphine-induced behavioral sensitization. Morphine treatment significantly elicited ERK phosphorylation and downregulated the expression level of α1 adrenoceptors in the VLO. In addition, intra-VLO benoxathian injection enhanced the expression levels of α1 adrenoceptors and phosphorylated ERK. These results suggest that α1 adrenoceptors in the VLO are involved in regulating the expression of morphine-induced behavioral sensitization. The effect of decreased locomotor activity by blocking α1 adrenoceptors might be associated with activation of ERK in the VLO. PMID:26520466

  7. Gastric pentadecapeptide BPC 157 counteracts morphine-induced analgesia in mice.

    PubMed

    Boban Blagaic, A; Turcic, P; Blagaic, V; Dubovecak, M; Jelovac, N; Zemba, M; Radic, B; Becejac, T; Stancic Rokotov, D; Sikiric, P

    2009-12-01

    Previously, the gastric pentadecapeptide BPC 157, (PL 14736, Pliva) has been shown to have several beneficial effects, it exert gastroprotective, anti-inflammatory actions, stimulates would healing and has therapeutic value in inflammatory bowel disease. The present study aimed to study the effect of naloxone and BPC 157 on morphine-induced antinociceptive action in hot plate test in the mouse. It was found that naloxone and BPC 157 counteracted the morphine (16 mg/kg s.c.) - analgesia. Naloxone (10 mg/kg s.c.) immediately antagonised the analgesic action and the reaction time returned to the basic values, the development of BPC 157-induced action (10 pg/kg, 10 ng/kg, 10 microg/kg i.p.) required 30 minutes. When haloperidol, a central dopamine-antagonist (1 mg/kg i.p.), enhanced morphine-analgesia, BPC 157 counteracted this enhancement and naloxone reestablished the basic values of pain reaction. BPC 157, naloxone, and haloperidol per se failed to exert analgesic action. In summary, interaction between dopamine-opioid systems was demonstrated in analgesia, BPC 157 counteracted the haloperidol-induced enhancement of the antinociceptive action of morphine, indicating that BPC acts mainly through the central dopaminergic system. PMID:20388962

  8. Role of phosphodiesterase inhibitor Ibudilast in morphine-induced hippocampal injury

    PubMed Central

    Zhaleh, Mohsen; Panahi, Marzieh; Ghafurian Broujerdnia, Mehri; Ghorbani, Rostam; Ahmadi Angali, Kambiz; Saki, Ghasem

    2014-01-01

    Abstract: Background: Opioid drugs are used in the treatment of acute post-surgical pain and chronic pain, such as those associated with cancer. Opioid used is associated with complications such as analgesic tolerance, dependence and opioid abuse. The molecular mechanisms of unwanted opioid responses are varied but recent advances have highlighted elevations in pro-inflammatory cytokines and pro-inflammatory glial following chronic administration of morphine. In this study we investigated the neurodegenerative effects of morphine through its effects on Toll-Like Receptor 4 (TLR4) in the male rat hippocampus and evaluated the level of Interleukin-1 beta (IL-1β). Then we compared the difference between inhibitory effects on mu opioid receptors (by β-Funaltrexamine, β-FNA) and TLR4 (by Ibudilast). Subsequently, we assessed the amount of IL-1β and the number of granular cells in male rat hippocampus. Methods: Adult male rats (n=24) were treated with sucrose, morphine, Ibudilast (7.5 mg/kg) and β-FNA (20 mg/kg) for 30 days. Their brains were isolated and hemisected with one hippocampus for granular cell and the other used for IL-1 β immunoblotting. Results: Data showed that Ibudilast suppresses IL-1 β expression significantly more than β-FNA. The granular cell count displayed significant differences. Conclusions: Our results suggested that Ibudilast can be used for controlling and treatment of morphine-induced CNS inflammations or traumatic conditions. PMID:24121451

  9. Blockade of Cannabinoid CB1 receptor attenuates the acquisition of morphine-induced conditioned place preference along with a downregulation of ERK, CREB phosphorylation, and BDNF expression in the nucleus accumbens and hippocampus.

    PubMed

    Zhang, Jianbo; Wang, Na; Chen, Bo; Wang, Yi'nan; He, Jing; Cai, Xintong; Zhang, Hongbo; Wei, Shuguang; Li, Shengbin

    2016-09-01

    Cannabinoid CB1 receptor (CB1R) is highly expressed in the mesocorticolimbic system and associated with drug craving and relapse. Clinical trials suggest that CB1R antagonists may represent new therapies for drug addiction. However, the downstream signaling of CB1R is not fully elucidated. In the present study, we investigated the relationship between CB1R and the extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF) signaling in the nucleus accumbens (NAc) and hippocampus in morphine-induced conditioned place preference (CPP), which is used to assess the morphine-induced reward memory. The protein level of CB1R, ERK, CREB, and BDNF were detected by western blotting. Additionally, a CB1R antagonist, AM251, was used to study whether blockade of CB1R altered the CPP and above-mentioned molecules. We found an increase of CB1R expression in the NAc and hippocampus of the mice following morphine CPP, but not those after repeated morphine in home cage without context exposure (NO-CPP). Both morphine CPP and NO-CPP induced an upregulation of ERK, CREB phosphorylation and BDNF expression. Furthermore, pretreatment with AM251 before morphine attenuated the CPP acquisition and CB1R expression as well as the activation of ERK-CREB-BDNF cascade. Collectively, these findings demonstrate that (1) Repeated morphine with context exposures but not merely the pharmacological effects of morphine increased CB1R expression both in the NAc and hippocampus. (2) CB1R antagonist mediated blockade of ERK-CREB-BDNF signaling activation in the NAc and hippocampus may be an important mechanism underlying the attenuation of morphine CPP. PMID:27461790

  10. CP-154,526 Modifies CREB Phosphorylation and Thioredoxin-1 Expression in the Dentate Gyrus following Morphine-Induced Conditioned Place Preference

    PubMed Central

    García-Carmona, Juan-Antonio; Camejo, Daymi M.; Almela, Pilar; Jiménez, Ana; Milanés, María-Victoria; Sevilla, Francisca; Laorden, María-Luisa

    2015-01-01

    Corticotropin-releasing factor (CRF) acts as neuro-regulator of the behavioral and emotional integration of environmental and endogenous stimuli associated with drug dependence. Thioredoxin-1 (Trx-1) is a functional protein controlling the redox status of several proteins, which is involved in addictive processes. In the present study, we have evaluated the role of CRF1 receptor (CRF1R) in the rewarding properties of morphine by using the conditioned place preference (CPP) paradigm. We also investigate the effects of the CRF1R antagonist, CP-154,526, on the morphine CPP-induced activation of CRF neurons, CREB phosphorylation and Trx expression in paraventricular nucleus (PVN) and dentate gyrus (DG) of the mice brain. CP-154,526 abolished the acquisition of morphine CPP and the increase of CRF/pCREB positive neurons in PVN. Moreover, this CRF1R antagonist prevented morphine-induced CRF-immunoreactive fibers in DG, as well as the increase in pCREB expression in both the PVN and DG. In addition, morphine exposure induced an increase in Trx-1 expression in DG without any alterations in PVN. We also observed that the majority of pCREB positive neurons in DG co-expressed Trx-1, suggesting that Trx-1 could activate CREB in the DG, a brain region involved in memory consolidation. Altogether, these results support the idea that CRF1R antagonist blocked Trx-1 expression and pCREB/Trx-1 co-localization, indicating a critical role of CRF, through CRF1R, in molecular changes involved in morphine associated behaviors. PMID:26313266

  11. Differential effects of gram-positive and gram-negative bacterial products on morphine induced inhibition of phagocytosis

    PubMed Central

    Jana, Ninkovic; Vidhu, Anand; Raini, Dutta; Zhang, Li; Saluja, Anuj; Meng, Jingjing; Lisa, Koodie; Santanu, Banerjee; Sabita, Roy

    2016-01-01

    Opioid drug abusers have a greater susceptibility to gram positive (Gram (+)) bacterial infections. However, the mechanism underlying opioid modulation of Gram (+) versus Gram (−) bacterial clearance has not been investigated. In this study, we show that opioid treatment resulted in reduced phagocytosis of Gram (+), when compared to Gram (−) bacteria. We further established that LPS priming of chronic morphine treated macrophages leads to potentiated phagocytosis and killing of both Gram (+) and Gram (−) bacteria in a P-38 MAP kinase dependent signaling pathway. In contrast, LTA priming lead to inhibition of both phagocytosis and bacterial killing. This study demonstrates for the first time the differential effects of TLR4 and TLR2 agonists on morphine induced inhibition of phagocytosis. Our results suggest that the incidence and severity of secondary infections with Gram (+) bacteria would be higher in opioid abusers. PMID:26891899

  12. Altering dietary levels of protein or vitamins and minerals does not modify morphine-induced analgesia in male rats.

    PubMed

    Kanarek, R B; D'Anci, K E; Przypek, J M; Mathes, W F

    1999-02-01

    Previous research has demonstrated that chronic intake of nutritive sweet solutions, but not nonnutritive sweet solutions, enhances morphine's analgesic potency. To separate out the effects of sweet taste from other changes in dietary intake, which result when rats consume a sucrose solution, the effects of altering dietary levels of protein, or vitamins and minerals on morphine-induced analgesia were examined. In Experiment 1, 40 male Long-Evans rats were fed standard chow or a semipurified diet containing either 10, 20, or 40% protein. Three weeks later, antinociceptive responses to morphine were examined using the tail flick procedure. Tail flick latencies were measured immediately prior to and 30, 60, and 90 min after the administration of morphine sulfate (0.0, 1.25, 2.5, and 5.0 mg/kg, SC). At all three measurement times, antinociceptive responses increased directly as a function of the dose of morphine, but did not differ as a function of diet. In Experiment 2, 24 rats were maintained on either standard laboratory chow or semipurified diets containing 20% protein and either 100% or 25% of the recommended levels of vitamins and minerals for 3 weeks. Tail flick latencies were measured immediately prior to and 30 min after injections (SC) of 2.5 mg/kg morphine sulfate. This procedure was repeated until a cumulative dose of 10.0 mg/kg was obtained. Tail flick latencies increased significantly as a function of drug dose, but did not differ across dietary conditions. These results demonstrate that the increase in morphine-induced analgesia seen in rats consuming a sucrose solution is not due to alterations in either protein or micronutrient intake. PMID:9972684

  13. Comparative study between nalbuphine and ondansetron in prevention of intrathecal morphine-induced pruritus in women undergoing cesarean section

    PubMed Central

    Moustafa, Ahmed A. M.; Baaror, Amr Samir; Abdelazim, Ibrahim A.

    2016-01-01

    Background: Intrathecal morphine provides effective postoperative analgesia, but their use is associated with numerous side effects, including pruritus, nausea, vomiting, urinary retention, and respiratory depression. Pruritus is the most common side effect with a reported incidence of 58–85%. Objectives: This prospective, randomized, and double-blinded study was performed for women scheduled for cesarean delivery using spinal anesthesia to compare nalbuphine and ondansetron in the prevention of intrathecal morphine-induced pruritus. Patients and Methods: Ninety women after spinal anesthesia with hyperbaric bupivacaine and intrathecal morphine patients randomly divided into three groups. Women in placebo group (P group) received 4 ml of normal saline intravenous (IV) injection, nalbuphine group (N group) received 4 ml of a 4 mg nalbuphine IV injection, and ondansetron 4 group (O group) received 4 ml of a 4 mg ondansetron IV injection, immediately after delivery of the baby. Studied women observed in postanesthesia care unit for 4 h. The primary outcome measures success of the treatment, defined as a pruritus score 1 (no pruritus) or 2 (mild pruritus - no treatment required) at 20 min after treatment. Results: Although, three was no significant difference between the three studied groups regarding; score 1 pruritus, while, score 2 pruritus (mild pruritus - no treatment requested) was significantly high in N and O groups compared to placebo group. Pruritus score 1 (no pruritus) plus pruritus score 2 were significantly high in N and O groups compared to placebo group (20 cases, 20 cases, 5 cases; respectively, P = 0.008). In addition; score 3 pruritus (moderate - treatment requested) was significantly less in N and O groups compared to placebo group. Conclusion: Nalbuphine and ondansetron were found to be more effective than placebo for prevention of intrathecal morphine-induced pruritus in women undergoing cesarean delivery and nalbuphine is preferred than

  14. α-Terpineol attenuates morphine-induced physical dependence and tolerance in mice: role of nitric oxide

    PubMed Central

    Parvardeh, Siavash; Moghimi, Mahsa; Eslami, Pegah; Masoudi, Alireza

    2016-01-01

    Objective(s): Dependence and tolerance to opioid analgesics are major problems limiting their clinical application. α-Terpineol is a monoterpenoid alcohol with neuroprotective effects which is found in several medicinal plants such as Myrtus communis, Laurus nobilis, and Stachys byzantina. It has been shown that some of these medicinal plants such as S. byzantina attenuate dependence and tolerance to morphine. Since α-terpineol is one of the bioactive phytochemical constituent of these medicinal plants, the present study was conducted to investigate the effects of α-terpineol on morphine-induced dependence and tolerance in mice. Materials and Methods: The mice were rendered dependent or tolerant to morphine by a 3-day administration schedule. The hot-plate test and naloxone-induced withdrawal syndrome were used to evaluate tolerance and dependence on morphine, respectively. To investigate a possible role for nitric oxide (NO) in the protective effect of α-terpineol, the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME) and NO precursor, L-arginine, were used. Results: Administration of α-terpineol (5, 10, and 20 mg/kg, IP) significantly decreased the number of jumps in morphine dependent animals. Moreover, α-terpineol (20 and 40 mg/kg, IP) attenuated tolerance to the analgesic effect of morphine. The inhibitory effects of α-terpineol on morphine-induced dependence and tolerance were enhanced by pretreatment with L-NAME (10 mg/kg, IP). However, L-arginine (300 mg/kg, IP) antagonized the protective effects of α-terpineol on dependence and tolerance to morphine. Conclusion: These findings indicate that α-terpineol prevents the development of dependence and tolerance to morphine probably through the influence on NO production. PMID:27081466

  15. Morphine-induced μ-Opioid Receptor Rapid Desensitization is independent of Receptor Phosphorylation and β-Arrestins

    PubMed Central

    Chu, Ji; Zheng, Hui; Loh, Horace H.; Law, Ping-Yee

    2008-01-01

    Receptor desensitization involving receptor phosphorylation and subsequent βArrestin (βArr) recruitment has been implicated in the tolerance development mediated by μ-opioid receptor (OPRM1). However, the roles of receptor phosphorylation and βArr on morphine-induced OPRM1 desensitization remain to be demonstrated. Using OPRM1-induced intracellular Ca2+ ([Ca2+]i )release to monitor receptor activation, as predicted, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), induced OPRM1 desensitization in a receptor phosphorylation- and βArr-dependent manner. The DAMGO-induced OPRM1 desensitization was attenuated significantly when phosphorylation deficient OPRM1 mutants or Mouse Embryonic Fibroblast (MEF) cells from βArr1 and 2 knockout mice were used in the studies. Specifically, DAMGO-induced desensitization was blunted in HEK293 cells expressing the OPRM1S375A mutant and was eliminated in MEF cells isolated from βArr2 knockout mice expressing the wild type OPRM1. However, although morphine also could induce a rapid desensitization on [Ca2+]i release to a greater extent than that of DAMGO and could induce the phosphorylation of Ser375 residue, morphine-induced desensitization was not influenced by mutating the phosphorylation sites or in MEF cells lacking βArr1 and 2. Hence, morphine could induce OPRM1 desensitization via pathway independent of βArr, thus suggesting the in vivo tolerance development to morphine can occur in the absence of βArr. PMID:18558479

  16. Beyond Rewards

    ERIC Educational Resources Information Center

    Hall, Philip S.

    2009-01-01

    Using rewards to impact students' behavior has long been common practice. However, using reward systems to enhance student learning conveniently masks the larger and admittedly more difficult task of finding and implementing the structure and techniques that children with special needs require to learn. More important, rewarding the child for good…

  17. Differences in the morphine-induced inhibition of small and large intestinal transit: Involvement of central and peripheral μ-opioid receptors in mice.

    PubMed

    Matsumoto, Kenjiro; Umemoto, Hiroyuki; Mori, Tomohisa; Akatsu, Ryuya; Saito, Shinichiro; Tashima, Kimihito; Shibasaki, Masahiro; Kato, Shinichi; Suzuki, Tsutomu; Horie, Syunji

    2016-01-15

    Constipation is the most common side effect of morphine. Morphine acts centrally and on peripheral sites within the enteric nervous system. There are a few comprehensive studies on morphine-induced constipation in the small and large intestine by the activation of central and peripheral μ-opioid receptors. We investigated the differences in the inhibition of the small and large intestinal transit in normal and morphine-tolerant mice. Morphine reduced the geometric center in the fluorescein isothiocyanate-dextran assay and prolonged the bead expulsion time in a dose-dependent manner. The inhibitory effects of morphine were blocked by μ-opioid antagonist β-funaltrexamine, but not by δ- and κ-opioid antagonists. The peripheral opioid receptor antagonist, naloxone methiodide, partially blocked morphine's effect in the small intestine and completely blocked its effect in the large intestine. The intracerebroventricular administration of naloxone significantly reversed the delay of small intestinal transit but did not affect morphine-induced inhibition of large intestinal transit. Naloxone methiodide completely reversed the inhibition of large intestinal transit in normal and morphine-tolerant mice. Naloxone methiodide partially reversed the morphine-induced inhibition of small intestinal transit in normal mice but completely reversed the effects of morphine in tolerant mice. Chronic treatment with morphine results in tolerance to its inhibitory effect on field-stimulated contraction in the isolated small intestine but not in the large intestine. These results suggest that peripheral and central opioid receptors are involved in morphine-induced constipation in the small and large intestine during the early stage of treatment, but the peripheral receptors mainly regulate constipation during long-term morphine treatment. PMID:26712376

  18. MicroRNA-219-5p Inhibits Morphine-Induced Apoptosis by Targeting Key Cell Cycle Regulator WEE1

    PubMed Central

    Lou, Wei; Zhang, Xingwang; Hu, Xiao-Ying; Hu, Ai-Rong

    2016-01-01

    Background To identify the effects of microRNA (miR)-219-5p on morphine-induced apoptosis by targeting WEE1. Material/Methods Forty Balb/C mice (Toll-like receptor 9, TLR9 knockout) were randomly allocated to the experimental and control groups (20 in each group). The baseline miR-219-5p expression was detected using quantitative real-time PCR (qRT-PCR). After morphine was injected at 6 h on the 2nd and 6th days, experimental and control groups received miR-219-5p mimics or miRNA-negative control (NC), respectively, compound injection. Tissues and cells were later obtained from subjects in each group separately after mice were killed. TUNEL assay was used to investigate apoptosis in both groups. RAW264.7 cells were treated with miR-219-5p mimics and controls, respectively. After 24 h, 10 μM of morphine was added at 24 h. Cell apoptosis was assessed by flow cytometer. The WEE1 and Phospho-cdc2 (Tyr15) expressions were examined by Western blotting. Results MiR-219-5p expression in the experimental group was significantly lower than that in the control group (P<0.05). Mice injected with miR-219-5p mimic experienced an evident increase in apoptosis rate compared with the control group (P<0.05). The miR-219-5p NC group and the morphine group both presented an elevated apoptosis rate compared with the blank control group (both, P<0.05). The apoptosis rate in the miR-219-5p mimic group was 10.06%, remarkably lower than in the miR-219-5p NC group and blank control group (both P<0.05). WEE1 and Tyr15 protein expressions in the miR-219-5p NC group and morphine group were obviously stronger than those in the blank control group (all P<0.05). In the miR-219-5p mimic group, WEE1 and Tyr15 protein expressions were significantly lower compared with those in the miR-219-5p NC group and morphine group (all P<0.05). Conclusions Morphine significantly downregulated the expression of miRNA-219-5p, which targets WEE1 to suppress Tyr15 expressions and activate Cdc2, thus inhibiting the

  19. MicroRNA-219-5p Inhibits Morphine-Induced Apoptosis by Targeting Key Cell Cycle Regulator WEE1.

    PubMed

    Lou, Wei; Zhang, Xingwang; Hu, Xiao-Ying; Hu, Ai-Rong

    2016-01-01

    BACKGROUND To identify the effects of microRNA (miR)-219-5p on morphine-induced apoptosis by targeting WEE1. MATERIAL AND METHODS Forty Balb/C mice (Toll-like receptor 9, TLR9 knockout) were randomly allocated to the experimental and control groups (20 in each group). The baseline miR-219-5p expression was detected using quantitative real-time PCR (qRT-PCR). After morphine was injected at 6 h on the 2nd and 6th days, experimental and control groups received miR-219-5p mimics or miRNA-negative control (NC), respectively, compound injection. Tissues and cells were later obtained from subjects in each group separately after mice were killed. TUNEL assay was used to investigate apoptosis in both groups. RAW264.7 cells were treated with miR-219-5p mimics and controls, respectively. After 24 h, 10 μM of morphine was added at 24 h. Cell apoptosis was assessed by flow cytometer. The WEE1 and Phospho-cdc2 (Tyr15) expressions were examined by Western blotting. RESULTS MiR-219-5p expression in the experimental group was significantly lower than that in the control group (P<0.05). Mice injected with miR-219-5p mimic experienced an evident increase in apoptosis rate compared with the control group (P<0.05). The miR-219-5p NC group and the morphine group both presented an elevated apoptosis rate compared with the blank control group (both, P<0.05). The apoptosis rate in the miR-219-5p mimic group was 10.06%, remarkably lower than in the miR-219-5p NC group and blank control group (both P<0.05). WEE1 and Tyr15 protein expressions in the miR-219-5p NC group and morphine group were obviously stronger than those in the blank control group (all P<0.05). In the miR-219-5p mimic group, WEE1 and Tyr15 protein expressions were significantly lower compared with those in the miR-219-5p NC group and morphine group (all P<0.05). CONCLUSIONS Morphine significantly downregulated the expression of miRNA-219-5p, which targets WEE1 to suppress Tyr15 expressions and activate Cdc2, thus inhibiting

  20. Comparative rewarding properties of morphine and butorphanol.

    PubMed

    Mamoon, A M; Barnes, A M; Ho, I K; Hoskins, B

    1995-01-01

    Because butorphanol (Stadol), a synthetic morphinan compound, has been demonstrated in our laboratories to produce physical dependence and withdrawal symptoms in rats, we have hypothesized that butorphanol has rewarding properties indicative of abuse potential. To test this hypothesis, the effects of equimolar doses of butorphanol tartrate (0.5-5.0 micrograms) and morphine sulfate (0.8-8.0 micrograms) were assessed in inbred Lewis male rats using the conditioned place preference (CPP) paradigm. Unilateral microinjections (1 microl/inj) of saline or opioids were made into the ventral tegmental area (VTA). Microinjections of saline to controls were associated with both sides of modified Skinner boxes, whereas opioid injections were associated only with the white chambers (less preferred side to the naive animals). Opioids were administered alternating with saline in the drug-treated animals on alternating days. During eight conditioning sessions the rats learned to associate light and dark sides of the Skinner boxes with microinjections of opioids or saline, respectively. Although all doses of morphine induced significant preference over saline, only the higher doses of butorphanol (2.0-5.0 micrograms) produced significant conditioned place preference for the sides of the chambers associated with the drugs. These results suggest that, like morphine which is widely abused, butorphanol also has rewarding properties, and, therefore, further investigations regarding its abuse potential are necessary. PMID:8665275

  1. The effect of alpha-interferon, cyclosporine A, and radiation-induced immune suppression on morphine-induced hypothermia and tolerance.

    PubMed

    Dougherty, P M; Harper, C; Dafny, N

    1986-12-01

    An interconnection between the immune and the central nervous systems has been suggested by investigators studying the actions of several types of immune modifying agents and procedures upon opiate related phenomena. These studies have included the effects of altering immune system function by administration of either alpha-interferon, cyclosporine or radiation exposure upon naloxone-precipitated opiate withdrawal and upon opioid antinociceptive effects. The present study extends these earlier investigations by examining the effect of immune modulation upon opiate induced hypothermia. The results demonstrate that interferon and cyclosporine have no effects on baseline temperature or morphine induced hypothermia, while irradiation exposure elicits hyperthermia without affecting morphine-induced hypothermia. Finally, neither cyclosporine nor irradiation affect the development of tolerance to morphine induced hypothermia, while a single injection of the immune system modifier interferon was able to prevent the development of such tolerance. These observations suggest that yet another opiate-related phenomenon may be regulated at least in part by the immune system. These results together with our previous findings are further evidence of a link between the immune system and the CNS mediated through the opioid system. In addition, these studies further support our earlier hypothesis that "Interferon" is one of the endogenous substances which serves to prevent the development of tolerance and dependence to endogenous opioids. PMID:3784774

  2. Inhibition of Spinal Oxidative Stress by Bergamot Polyphenolic Fraction Attenuates the Development of Morphine Induced Tolerance and Hyperalgesia in Mice

    PubMed Central

    Lauro, Filomena; Giancotti, Luigino Antonio; Ilari, Sara; Dagostino, Concetta; Gliozzi, Micaela; Morabito, Chiara; Malafoglia, Valentina; Raffaeli, William; Muraca, Maurizio; Goffredo, Bianca M.; Mollace, Vincenzo; Muscoli, Carolina

    2016-01-01

    Citrus Bergamia Risso, commonly known as Bergamot, is a fruit whose Essential Oil and Bergamot Polyphenolic Fraction have numerous medicinal properties. It is also an excellent antioxidant and in this study, for the first time, its potential effect on morphine induced tolerance in mice has been investigated. Our studies revealed that development of antinociceptive tolerance to repeated doses of morphine in mice is consistently associated with increased formation of superoxide, malondialdehyde and tyrosine-nitrated proteins in the dorsal horn of the spinal cord such as the enzyme glutamine synthase. Nitration of this protein is intimately linked to inactivation of its biological function and resulting increase of glutamate levels in the spinal cord. Administration of Bergamot Polyphenolic Fraction (5–50 mg/kg) attenuated tolerance development. This effect was accompanied by reduction of superoxide and malondialdehyde production, prevention of GS nitration, re-establishment of its activity and of glutamate levels. Our studies confirmed the main role of free radicals during the cascade of events induced by prolonged morphine treatment and the co-administration of natural derivatives antioxidant such as Bergamot Polyphenolic Fraction can be an important therapeutic approach to restore opioids analgesic efficacy. PMID:27227548

  3. Assessment of morphine-induced hyperalgesia and analgesic tolerance in mice using thermal and mechanical nociceptive modalities.

    PubMed

    Elhabazi, Khadija; Ayachi, Safia; Ilien, Brigitte; Simonin, Frédéric

    2014-01-01

    Opioid-induced hyperalgesia and tolerance severely impact the clinical efficacy of opiates as pain relievers in animals and humans. The molecular mechanisms underlying both phenomena are not well understood and their elucidation should benefit from the study of animal models and from the design of appropriate experimental protocols. We describe here a methodological approach for inducing, recording and quantifying morphine-induced hyperalgesia as well as for evidencing analgesic tolerance, using the tail-immersion and tail pressure tests in wild-type mice. As shown in the video, the protocol is divided into five sequential steps. Handling and habituation phases allow a safe determination of the basal nociceptive response of the animals. Chronic morphine administration induces significant hyperalgesia as shown by an increase in both thermal and mechanical sensitivity, whereas the comparison of analgesia time-courses after acute or repeated morphine treatment clearly indicates the development of tolerance manifested by a decline in analgesic response amplitude. This protocol may be similarly adapted to genetically modified mice in order to evaluate the role of individual genes in the modulation of nociception and morphine analgesia. It also provides a model system to investigate the effectiveness of potential therapeutic agents to improve opiate analgesic efficacy. PMID:25145878

  4. Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

    PubMed Central

    Elhabazi, Khadija; Ayachi, Safia; Ilien, Brigitte; Simonin, Frédéric

    2014-01-01

    Opioid-induced hyperalgesia and tolerance severely impact the clinical efficacy of opiates as pain relievers in animals and humans. The molecular mechanisms underlying both phenomena are not well understood and their elucidation should benefit from the study of animal models and from the design of appropriate experimental protocols. We describe here a methodological approach for inducing, recording and quantifying morphine-induced hyperalgesia as well as for evidencing analgesic tolerance, using the tail-immersion and tail pressure tests in wild-type mice. As shown in the video, the protocol is divided into five sequential steps. Handling and habituation phases allow a safe determination of the basal nociceptive response of the animals. Chronic morphine administration induces significant hyperalgesia as shown by an increase in both thermal and mechanical sensitivity, whereas the comparison of analgesia time-courses after acute or repeated morphine treatment clearly indicates the development of tolerance manifested by a decline in analgesic response amplitude. This protocol may be similarly adapted to genetically modified mice in order to evaluate the role of individual genes in the modulation of nociception and morphine analgesia. It also provides a model system to investigate the effectiveness of potential therapeutic agents to improve opiate analgesic efficacy. PMID:25145878

  5. Inhibition of Spinal Oxidative Stress by Bergamot Polyphenolic Fraction Attenuates the Development of Morphine Induced Tolerance and Hyperalgesia in Mice.

    PubMed

    Lauro, Filomena; Giancotti, Luigino Antonio; Ilari, Sara; Dagostino, Concetta; Gliozzi, Micaela; Morabito, Chiara; Malafoglia, Valentina; Raffaeli, William; Muraca, Maurizio; Goffredo, Bianca M; Mollace, Vincenzo; Muscoli, Carolina

    2016-01-01

    Citrus Bergamia Risso, commonly known as Bergamot, is a fruit whose Essential Oil and Bergamot Polyphenolic Fraction have numerous medicinal properties. It is also an excellent antioxidant and in this study, for the first time, its potential effect on morphine induced tolerance in mice has been investigated. Our studies revealed that development of antinociceptive tolerance to repeated doses of morphine in mice is consistently associated with increased formation of superoxide, malondialdehyde and tyrosine-nitrated proteins in the dorsal horn of the spinal cord such as the enzyme glutamine synthase. Nitration of this protein is intimately linked to inactivation of its biological function and resulting increase of glutamate levels in the spinal cord. Administration of Bergamot Polyphenolic Fraction (5-50 mg/kg) attenuated tolerance development. This effect was accompanied by reduction of superoxide and malondialdehyde production, prevention of GS nitration, re-establishment of its activity and of glutamate levels. Our studies confirmed the main role of free radicals during the cascade of events induced by prolonged morphine treatment and the co-administration of natural derivatives antioxidant such as Bergamot Polyphenolic Fraction can be an important therapeutic approach to restore opioids analgesic efficacy. PMID:27227548

  6. Examinations of the reward comparison hypothesis: The modulation of gender and footshock.

    PubMed

    Huang, Andrew Chih Wei; Wang, Cheng Chung; Wang, Shiun

    2015-11-01

    The reward comparison hypothesis suggests that drugs of abuse-induced conditioned saccharin suppression intake is due to the reward value of drugs of abuse that outweighs that of a saccharin solution dissociating from the aversive LiCl-induced conditioned taste aversion (CTA). Huang and Hsiao (2008) provided some conflict data to challenge the reward comparison hypothesis. Whether the rewarding drugs of abuse-induced conditioned suppression and the aversive LiCl-induced CTA resulted from aversion or reward should be addressed. The present study investigated how gender and footshock affect aversive LiCl- and rewarding morphine- and methamphetamine (MAMPH)-induced conditioned suppression to re-examine the reward comparison hypothesis. The results indicated that gender and footshock did not directly influence the aversive LiCl-induced CTA or rewarding morphine- and MAMPH-induced conditioned suppression. The gender effect interacted with the drug effect in the aversive LiCl- and rewarding MAMPH-induced conditioned suppression but did not interact with the drug effect in the rewarding morphine-induced conditioned suppression. Footshock interacted with the drug effect in rewarding morphine- and MAMPH-induced conditioned suppression, but footshock did not interact with the drug effect in the aversive LiCl-induced CTA. Therefore, the gender and footshock effects might play a modulatory (but not a mediating) role with the drug effect. The present data indicated that footshock modulates drugs of abuse-induced conditioned suppression, which is consistent with the reward comparison hypothesis, but our findings with regard to the modulatory role of the gender effect and the drug effect do not support this hypothesis. The reward comparison hypothesis should be discussed and possibly reconsidered. PMID:26192710

  7. Morphine-induced delayed pre-conditioning against anoxia/reoxygenation injury in pulmonary artery endothelial cells: The role of mitochondrial KATP channels.

    PubMed

    Ding, Wengang; Guo, Yueping; Cui, Xiaoguang; Zhang, Bing; Li, Dongmei; Li, Wenzhi

    2016-01-01

    Opioids produce delayed pre-conditioning (PC) in vivo and in vitro. Our previous research revealed that opioid‑induced delayed PC has an antiapoptotic effect on pulmonary artery endothelial cells (PAECs) suffering from anoxia/reoxygenation (A/R) injury. The present study hypothesized that activation of endothelial mitochondrial ATP‑sensitive potassium (KATP) channels may result in antiapoptotic effects and against dysfunction in PAECs. Cultured porcine PAECs underwent 16 h anoxia treatment, followed by 1 h reoxygenation, which occurred 24 h following pretreatment with saline (0.9% NaCl; w/v) or morphine (1 µM). To determine the underlying mechanism, a selective mitochondrial KATP inhibitor, 5‑hydroxydecanoic acid (5‑HD; 100 µM), and an opioid receptor antagonist, naloxone (Nal; 10 µM), were administered 30 min prior to the A/R load. The percentage of apoptotic cells was assessed by Annexin V‑fluorescein isothiocyanate staining, using a fluorescence‑activated cell sorter. The mRNA expression of intercellular cell adhesion molecule‑1 (ICAM‑1) was measured by reverse transcription‑quantitative polymerase chain reaction. The endothelin‑1 (ET‑1) content in the supernatant of PAECs cultures was estimated by radioimmunoassay. Compared with the control, A/R caused the apoptosis of PAECs, release of ET‑1 and increased mRNA expression of ICAM‑1. Morphine‑induced delayed PC significantly reduced PAEC apoptosis, increased the release of ET‑1 and reduced the mRNA expression of ICAM‑1 by ~1.7‑times, compared with A/R. The protective effect of morphine was abolished by pretreatment with 5‑HD and Nal, however, the two agents themselves failed to aggravate the A/R injury. These results suggested that morphine-induced delayed PC has a protective effect during A/R injury of PAECs. This effect may be mediated by mitochondrial KATP channels and is opioid receptor-dependent. PMID:26648415

  8. Neuro-Genetics of Reward Deficiency Syndrome (RDS) as the Root Cause of “Addiction Transfer”: A New Phenomenon Common after Bariatric Surgery

    PubMed Central

    Blum, Kenneth; Bailey, John; Gonzalez, Anthony M; Oscar-Berman, Marlene; Liu, Yijun; Giordano, John; Braverman, Eric; Gold, Mark

    2012-01-01

    Now after many years of successful bariatric (weight-loss) surgeries directed at the obesity epidemic clinicians are reporting that some patients are replacing compulsive overeating with newly acquired compulsive disorders such as alcoholism, gambling, drugs, and other addictions like compulsive shopping and exercise. This review article explores evidence from psychiatric genetic animal and human studies that link compulsive overeating and other compulsive disorders to explain the phenomenon of addiction transfer. Possibly due to neurochemical similarities, overeating and obesity may act as protective factors reducing drug reward and addictive behaviors. In animal models of addiction withdrawal from sugar induces imbalances in the neurotransmitters, acetylcholine and dopamine, similar to opiate withdrawal. Many human neuroimaging studies have supported the concept of linking food craving to drug craving behavior. Previously our laboratory coined the term Reward Deficiency Syndrome (RDS) for common genetic determinants in predicting addictive disorders and reported that the predictive value for future RDS behaviors in subjects carrying the DRD2 Taq A1 allele was 74%. While poly genes play a role in RDS, we have also inferred that disruptions in dopamine function may predispose certain individuals to addictive behaviors and obesity. It is now known that family history of alcoholism is a significant obesity risk factor. Therefore, we hypothesize here that RDS is the root cause of substituting food addiction for other dependencies and potentially explains this recently described Phenomenon (addiction transfer) common after bariatric surgery. PMID:23483116

  9. Morphine-induced internalization of the L83I mutant of the rat μ-opioid receptor

    PubMed Central

    Cooke, A E; Oldfield, S; Krasel, C; Mundell, S J; Henderson, G; Kelly, E

    2015-01-01

    BACKGROUND AND PURPOSE Naturally occurring single-nucleotide polymorphisms (SNPs) within GPCRs can result in alterations in various pharmacological parameters. Understanding the regulation and function of endocytic trafficking of the μ-opioid receptor (MOP receptor) is of great importance given its implication in the development of opioid tolerance. This study has compared the agonist-dependent trafficking and signalling of L83I, the rat orthologue of a naturally occurring variant of the MOP receptor. EXPERIMENTAL APPROACH Cell surface elisa, confocal microscopy and immunoprecipitation assays were used to characterize the trafficking properties of the MOP-L83I variant in comparison with the wild-type receptor in HEK 293 cells. Functional assays were used to compare the ability of the L83I variant to signal to several downstream pathways. KEY RESULTS Morphine-induced internalization of the L83I MOP receptor was markedly increased in comparison with the wild-type receptor. The altered trafficking of this variant was found to be specific to morphine and was both G-protein receptor kinase- and dynamin-dependent. The enhanced internalization of L83I variant in response to morphine was not due to increased phosphorylation of serine 375, arrestin association or an increased ability to signal. CONCLUSIONS AND IMPLICATIONS These results suggest that morphine promotes a specific conformation of the L83I variant that makes it more liable to internalize in response to morphine, unlike the wild-type receptor that undergoes significantly less morphine-stimulated internalization, providing an example of a ligand-selective biased receptor. The presence of this SNP within an individual may consequently affect the development of tolerance and analgesic responses. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24697554

  10. Role of hippocampal and prefrontal cortical signaling pathways in dextromethorphan effect on morphine-induced memory impairment in rats.

    PubMed

    Ghasemzadeh, Zahra; Rezayof, Ameneh

    2016-02-01

    Evidence suggests that dextromethorphan (DM), an NMDA receptor antagonist, induces memory impairment. Considering that DM is widely used in cough-treating medications, and the co-abuse of DM with morphine has recently been reported, the aims of the present study was (1) to investigate whether there is a functional interaction between morphine and DM in passive avoidance learning and (2) to assess the possible role of the hippocampal and prefrontal cortical (PFC) signaling pathways in the effects of the drugs on memory formation. Our findings indicated that post-training or pre-test administration of morphine (2 and 6 mg/kg) or DM (10-30 mg/kg) impaired memory consolidation and retrieval which was associated with the attenuation of the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (p-CAMKII) and cAMP responsive element-binding protein (p-CREB) in the targeted sites. Moreover, the memory impairment induced by post-training administration of morphine was reversed by pre-test administration of the same dose of morphine or DM (30 mg/kg), indicating state-dependent learning (SDL) and a cross-SDL between the drugs. It is important to note that the levels of p-CAMKII/CAMKII and p-CREB/CREB in the hippocampus and the PFC increased in drugs-induced SDL. In addition, DM administration potentiated morphine-induced SDL which was related to the enhanced levels of hippocampal and PFC CAMKII-CREB signaling pathways. It can be concluded that there is a relationship between the hippocampus and the PFC in the effect of DM and/or morphine on memory retrieval. Moreover, a cross SDL can be induced between the co-administration of DM and morphine. Interestingly, CAMKII-CREB signaling pathways also mediate the drugs-induced SDL. PMID:26708494

  11. AN IL-1 RECEPTOR ANTAGONIST BLOCKS A MORPHINE-INDUCED ATTENUATION OF LOCOMOTOR RECOVERY AFTER SPINAL CORD INJURY

    PubMed Central

    Hook, Michelle A.; Washburn, Stephanie N.; Moreno, Georgina; Woller, Sarah A.; Puga, Denise; Lee, Kuan H.; Grau, James W.

    2010-01-01

    Morphine is one of the most commonly prescribed medications for the treatment of chronic pain after a spinal cord injury (SCI). Despite widespread use, however, little is known about the secondary consequences of morphine use after SCI. Unfortunately, our previous studies show that administration of a single dose of morphine, in the acute phase of a moderate spinal contusion injury, significantly attenuates locomotor function, reduces weight gain, and produces symptoms of paradoxical pain (Hook et al., 2009). The current study focused on the cellular mechanisms that mediate these effects. Based on data from other models, we hypothesized that pro-inflammatory cytokines might play a role in the morphine-induced attenuation of function. Experiment 1 confirmed that systemic morphine (20 mg/kg) administered one day after a contusion injury significantly increased expression levels of spinal IL-1β 24 hrs later. Experiment 2 extended these findings, demonstrating that a single dose of morphine (90 µg, i.t.) applied directly onto the spinal cord increased expression levels of spinal IL-1β at both 30 min and 24 hrs after administration. Experiment 3 showed that administration of an interleukin-1 receptor antagonist (IL-1ra, i.t.) prior to intrathecal morphine (90 µg), blocked the adverse effects of morphine on locomotor recovery. Further, pre-treatment with 3 µg IL-1ra prevented the increased expression of at-level neuropathic pain symptoms that was observed 28 days later in the group treated with morphine-alone. However, the IL-1ra also had adverse effects that were independent of morphine. Treatment with the IL-1ra alone undermined recovery of locomotor function, potentiated weight loss and significantly increased tissue loss at the injury site. Overall, these data suggest that morphine disrupts a critical balance in concentrations of pro-inflammatory cytokines in the spinal cord, and this undermines recovery of function. PMID:20974246

  12. Involvement of protein kinase C in the modulation of morphine-induced analgesia and the inhibitory effects of exposure to 60-hz magnetic fields in the land snail, Cepaea nemoralis

    SciTech Connect

    Kavaliers, M.; Ossenkopp, K.P. )

    1990-02-26

    One of the more consistent and dramatic effects of exposure to magnetic fields is the attenuation of morphine-induced analgesia. Results of previous studies have implicated alterations in calcium channel functioning and Ca{sup ++} flux in the mediation of these effects. It is generally accepted that Ca{sup ++}-activated-phospholipid-dependent protein kinase (Protein kinase C; PKC) plays an important role in relaying trans-membrane signaling in diverse Ca{sup ++} dependent cellular processes. In experiment 1 we observed that morphine-induced analgesia in the land snail, Cepaea nemoralis, as measured by the latency of an avoidance behavior to a warmed surface, was reduced by the PKC activator, SC-9, and was enhanced by the PKC inhibitors, H-7 and H-9. In contrast, HA-10004, a potent inhibitor of other protein kinases, but only a very weak inhibitor of PKC, had no effect on morphine-induced analgesia. In experiment 2 exposure of snails for 30 minutes to a 1.0 gauss (rms) 60-Hz magnetic field reduced morphine-induced analgesia. This inhibitory effect of the magnetic field was reduced by the PKC inhibitors, H-7 and H-9, and was augmented by the PKC activator SC-9. These results suggest that: (i) PKC is involved in the modulation of morphine-induced analgesia and, (ii) the inhibitory effects of magnetic fields involve PKC.

  13. Managing morphine-induced constipation: a controlled comparison of an Ayurvedic formulation and senna.

    PubMed

    Ramesh, P R; Kumar, K S; Rajagopal, M R; Balachandran, P; Warrier, P K

    1998-10-01

    Constipation is a frequent cause of distress in advanced cancer. A palliative care unit in Kerala, a southern state of India, conducted a controlled trial comparing a liquid Ayurvedic (herbal) preparation (Misrakasneham) with a conventional laxative tablet (Sofsena) in the management of opioid-induced constipation in patients with advanced cancer. Although there was no statistically significant difference in the apparent degree of laxative action between the two, the results indicate that the small volume of the drug required for effective laxative action, the tolerable taste, the once-daily dose, the acceptable side effect profile, and the low cost make Misrakasneham a good choice for prophylaxis in opioid-induced constipation. There is a need for further studies of Ayurvedic medicines in palliative care. PMID:9803051

  14. GluR2-3Y Inhibits the Acquisition and Reinstatement of Morphine-Induced Conditioned Place Preference in Rats.

    PubMed

    Lin, Xiao-Jing; Zhang, Jian-Jun; Yu, Long-Chuan

    2016-04-01

    Accumulating evidence indicates that α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) are involved in the relapse to abused drugs. However, the role of AMPARs containing the GluR2 subunit in opiate addiction is still unclear. GluR2-3Y, an interfering peptide, prevents the endocytosis of AMPARs containing the GluR2 subunit. In this study, we explored the effect of intravenous injection of GluR2-3Y on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (mCPP) in rats. We found that infusion of GluR2-3Y (1.5 nmol/g) one hour before morphine during the conditioning phase inhibited the acquisition of mCPP, while an identical injection one hour before the post-conditioning test had no influence on the expression of mCPP. Injection of GluR2-3Y (1.5 nmol/g) after mCPP extinction blocked the morphine-induced reinstatement of mCPP. Our results strongly support the hypothesis that inhibition of AMPAR endocytosis provides a new target for the treatment of opiate addiction. PMID:26924808

  15. Prohormone convertase 2 (PC2) null mice have increased mu opioid receptor levels accompanied by altered morphine-induced antinociception, tolerance and dependence.

    PubMed

    Lutfy, K; Parikh, D; Lee, D L; Liu, Y; Ferrini, M G; Hamid, A; Friedman, T C

    2016-08-01

    Chronic morphine treatment increases the levels of prohormone convertase 2 (PC2) in brain regions involved in nociception, tolerance and dependence. Thus, we tested if PC2 null mice exhibit altered morphine-induced antinociception, tolerance and dependence. PC2 null mice and their wild-type controls were tested for baseline hot plate latency, injected with morphine (1.25-10mg/kg) and tested for antinociception 30min later. For tolerance studies, mice were tested in the hot plate test before and 30min following morphine (5mg/kg) on day 1. Mice then received an additional dose so that the final dose of morphine was 10mg/kg on this day. On days 2-4, mice received additional doses of morphine (20, 40 and 80mg/kg on days 1, 2, 3, and 4, respectively). On day 5, mice were tested in the hot plate test before and 30min following morphine (5mg/kg). For withdrawal studies, mice were treated with the escalating doses of morphine (10, 20, 40 and 80mg/kg) for 4days, implanted with a morphine pellet on day 5 and 3 days later injected with naloxone (1mg/kg) and signs of withdrawal were recorded. Morphine dose-dependently induced antinociception and the magnitude of this response was greater in PC2 null mice. Tolerance to morphine was observed in wild-type mice and this phenomenon was blunted in PC2 null mice. Withdrawal signs were also reduced in PC2 null mice. Immunohistochemical studies showed up-regulation of the mu opioid receptor (MOP) protein expression in the periaqueductal gray area, ventral tegmental area, lateral hypothalamus, medial hypothalamus, nucleus accumbens, and somatosensory cortex in PC2 null mice. Likewise, naloxone specific binding was increased in the brains of these mice compared to their wild-type controls. The results suggest that the PC2-derived peptides may play a functional role in morphine-induced antinociception, tolerance and dependence. Alternatively, lack of opioid peptides led to up-regulation of the MOP and altered morphine-induced

  16. Minocycline prevents morphine-induced apoptosis in rat cerebral cortex and lumbar spinal cord: a possible mechanism for attenuating morphine tolerance.

    PubMed

    Hassanzadeh, Kambiz; Habibi-asl, Bohlool; Farajnia, Safar; Roshangar, Leila

    2011-05-01

    Tolerance to the chronic administration of opioids such as morphine reduces the utility of these drugs in pain management. Despite significant investigation, the precise cellular mechanisms underlying opioid tolerance and dependence remain elusive. It has been indicated that tolerance to the analgesic effect of morphine is associated with apoptosis in the central nervous system. The aim of this study was to examine the effects of the intracerebroventricular (icv) administration of minocycline (a second-generation tetracycline) on morphine-induced apoptosis in the cerebral cortex and lumbar spinal cord of rats after morphine-induced tolerance. Different groups of rats received either morphine (ip) and distilled water (icv) or morphine and different doses of minocycline (icv) or minocycline alone once per day. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. The anti-apoptotic factors, Bcl-2 and HSP 70 and the pro-apoptotic element caspase-3 were evaluated by immunoblotting. The results indicated that minocycline attenuated the number of apoptotic cells in both the cerebral cortex and lumbar spinal cord. Immunoblotting findings showed that the amounts of anti-apoptotic agents (Bcl-2 and HSP 70) were greater in the treatment groups than in the controls in both regions. Although minocycline did not change the level of caspase-3 at the doses used with morphine but the minocycline treated rats showed a significantly lower increase in caspase-3 activity than did in the control. In conclusion, minocycline decreased the number of TUNEL-positive cells and increased the amount of anti-apoptotic factors (Bcl-2 and HSP 70), but did not change the caspase-3 content. PMID:20711699

  17. Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex

    PubMed Central

    Ahmadi, Shamseddin; Rafieenia, Fatemeh; Rostamzadeh, Jalal

    2016-01-01

    Introduction: Morphine is a potent analgesic but its continual use results in analgesic tolerance. Mechanisms of this tolerance remain to be clarified. However, changes in the functions of μ-opioid and N-Methyl-D-aspartate (NMDA) receptors have been proposed in morphine tolerance. We examined changes in gene expression of the NMDA receptor subunit 1 (NR1) at mRNA levels in rat striatum and prefrontal cortex (PFC) after induction of morphine tolerance. Methods: Morphine (10 mg/kg, IP) was injected in male Wistar rats for 7 consecutive days (intervention group), but control rats received just normal saline (1 mL/kg, IP). We used a hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days 1 and 8 of injections. Later, two groups of rats were sacrificed one day after 7 days of injections, their whole brains removed, and the striatum and PFC immediately dissected. Then, the NR1 gene expression was examined with a semi-quantitative RT-PCR method. Results: The results showed that long-term morphine a administration induces tolerance to analgesic effect of the opioid, as revealed by a significant decrease in morphine-induced analgesia on day 8 compared to day 1 of the injections (P<0.001). The results also showed that the NR1 gene expression at mRNA level in rats tolerant to morphine was significantly increased in the striatum (P<0.01) but decreased in the PFC (P<0.001). Conclusion: Therefore, changes in the NR1 gene expression in rat striatum and PFC have a region-specific association with morphine-induced analgesic tolerance. PMID:27563417

  18. Ventral Pallidum Roles in Reward and Motivation

    PubMed Central

    Smith, Kyle S.; Tindell, Amy J.; Aldridge, J. Wayne; Berridge, Kent C.

    2008-01-01

    In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that 1) an intact ventral pallidum is necessary for normal reward and motivation, 2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and 3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important ‘limbic final common pathway’ for mesocorticolimbic processing of many rewards. PMID:18955088

  19. Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?

    PubMed

    Blum, Kenneth; Chen, Thomas J H; Bailey, John; Bowirrat, Abdalla; Femino, John; Chen, Amanda L C; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R; Fornari, Frank; Downs, B William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

    2011-12-01

    Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence, the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research, the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate that buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that, to date, this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target

  20. Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?

    PubMed Central

    Blum, Kenneth; Chen, Thomas JH; Bailey, John; Bowirrat, Abdulla; Femino, John; Chen, Amanda LC; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R.; Fornari, Frank; Downs, B.William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

    2013-01-01

    Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that to date this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the

  1. The Rewards of Learning.

    ERIC Educational Resources Information Center

    Chance, Paul

    1992-01-01

    Although intrinsic rewards are important, they (along with punishment and encouragement) are insufficient for efficient learning. Teachers must supplement intrinsic rewards with extrinsic rewards, such as praising, complimenting, applauding, and providing other forms of recognition for good work. Teachers should use the weakest reward required to…

  2. Neurokinin1 receptors regulate morphine-induced endocytosis and desensitization of mu opioid receptors in CNS neurons

    PubMed Central

    Yu, Y. Joy; Arttamangkul, Seksiri; Evans, Christopher J.; Williams, John T.; von Zastrow, Mark

    2009-01-01

    Mu opioid receptors (MORs) are G protein-coupled receptors (GPCRs) that mediate the physiological effects of endogenous opioid neuropeptides and opiate drugs such as morphine. MORs are co-expressed with neurokinin 1 receptors (NK1Rs) in several regions of the central nervous system (CNS) that control opioid dependence and reward. NK1R activation affects opioid reward specifically, however, and the cellular basis for this specificity is unknown. We found that ligand-induced activation of NK1Rs produces a cell autonomous and non-reciprocal inhibition of MOR endocytosis induced by diverse opioids. Studies using epitope-tagged receptors expressed in cultured striatal neurons and a neuroblastoma cell model indicated that this heterologous regulation is mediated by NK1R-dependent sequestration of arrestins on endosome membranes. First, endocytic inhibition mediated by wild type NK1Rs was overcome in cells over-expressing β-arrestin2, a major arrestin isoform expressed in striatum. Second, NK1R activation promoted sequestration of β-arrestin2 on endosomes, whereas MOR activation did not. Third, heterologous inhibition of MOR endocytosis was prevented by mutational disruption of β-arrestin2 sequestration by NK1Rs. NK1R-mediated regulation of MOR trafficking was associated with reduced opioid-induced desensitization of adenylyl cyclase signaling in striatal neurons. Further, heterologous regulation of MOR trafficking was observed in both amygdala and locus coeruleus neurons that naturally co-express these receptors. These results identify a cell autonomous mechanism that may underlie the highly specific effects of NK1R on opioid signaling and suggest, more generally, that receptor-specific trafficking of arrestins may represent a fundamental mechanism for coordinating distinct GPCR-mediated signals at the level of individual CNS neurons. PMID:19129399

  3. STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance.

    PubMed

    Kim, Yoon-Jung; Kang, Young; Park, Hye-Yeon; Lee, Jae-Ran; Yu, Dae-Yeul; Murata, Takuya; Gondo, Yoichi; Hwang, Jung Hwan; Kim, Yong-Hoon; Lee, Chul-Ho; Rhee, Myungchull; Han, Pyung-Lim; Chung, Bong-Hyun; Lee, Hyun-Jun; Kim, Kyoung-Shim

    2016-01-01

    Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEP(C230X-/-) mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEP(C230X-/-) mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine. PMID:26915673

  4. STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance

    PubMed Central

    Kim, Yoon-Jung; Kang, Young; Park, Hye-Yeon; Lee, Jae-Ran; Yu, Dae-Yeul; Murata, Takuya; Gondo, Yoichi; Hwang, Jung Hwan; Kim, Yong-Hoon; Lee, Chul-Ho; Rhee, Myungchull; Han, Pyung-Lim; Chung, Bong-Hyun; Lee, Hyun-Jun; Kim, Kyoung-Shim

    2016-01-01

    Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEPC230X−/− mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEPC230X−/− mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine. PMID:26915673

  5. Real and hypothetical rewards.

    PubMed

    Locey, Matthew L; Jones, Bryan A; Rachlin, Howard

    2011-08-01

    Laboratory studies of choice and decision making among real monetary rewards typically use smaller real rewards than those common in real life. When laboratory rewards are large, they are almost always hypothetical. In applying laboratory results meaningfully to real-life situations, it is important to know the extent to which choices among hypothetical rewards correspond to choices among real rewards and whether variation of the magnitude of hypothetical rewards affects behavior in meaningful ways. The present study compared real and hypothetical monetary rewards in two experiments. In Experiment 1, participants played a temporal discounting game that incorporates the logic of a repeated prisoner's-dilemma (PD) type game versus tit-for-tat; choice of one alternative ("defection" in PD terminology) resulted in a small-immediate reward; choice of the other alternative ("cooperation" in PD terminology) resulted in a larger reward delayed until the following trial. The larger-delayed reward was greater for half of the groups than for the other half. Rewards also differed in type across groups: multiples of real nickels, hypothetical nickels or hypothetical hundred-dollar bills. All groups significantly increased choice of the larger delayed reward over the 40 trials of the experiment. Over the last 10 trials, cooperation was significantly higher when the difference between larger and smaller hypothetical rewards was greater. Reward type (real or hypothetical) made no significant difference in cooperation. In Experiment 2, real and hypothetical rewards were compared in social discounting - the decrease in value to the giver of a reward as social distance increases to the receiver of the reward. Social discount rates were well described by a hyperbolic function. Discounting rates for real and hypothetical rewards did not significantly differ. These results add to the evidence that results of experiments with hypothetical rewards validly apply in everyday life. PMID

  6. Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents

    PubMed Central

    Chidambaran, V; Mavi, J; Esslinger, H; Pilipenko, V; Martin, LJ; Zhang, K; Sadhasivam, S

    2015-01-01

    The μ1 opioid receptor (OPRM1) genetic variant A118G results in decreased μ-receptor binding potential in the brain and increases morphine requirement. We hypothesized that OPRM1 A118G polymorphism will affect morphine-induced respiratory depression (MIRD) risk in children receiving morphine. A prospective genotype-blinded study was conducted in 88 healthy adolescents (11–18 years; 67% female, 85% Caucasian) who underwent spine fusion for scoliosis. They were followed for 48 h postoperatively for MIRD, pain scores, morphine consumption and use of analgesic adjuvants. Patients were genotyped for OPRM1 A118G variant—76% were wild type (AA) and 24% heterozygous/homozygous for variant (AG/GG). Multivariable logistic regression showed that the risk of MIRD in patients with AA genotype was significantly higher (odds ratio 5.6, 95% CI: 1.4–37.2, P = 0.030). Presence of G allele was associated with higher pain scores (effect size 0.73, P = 0.045). This novel association is an important step toward predicting MIRD susceptibility and personalizing morphine use. PMID:25266679

  7. Okadaic acid blocks the effects of 5-aza-2-deoxycytidine on consolidation, acquisition and retrieval of morphine-induced place preference in rats.

    PubMed

    Zhang, Jian-Jun; Han, Jin; Sui, Nan

    2014-11-01

    Recent studies indicated that epigenetic modification, especially DNA methylation, play an important role in the persistence of addiction-related memory. 5-aza-2-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases, was approved for clinical treatment. However, it is not clear whether 5-aza is involved in opiate addiction. In this study, using the morphine-induced conditioned place preference (mCPP) model in rats, we injected 5-aza into hippocampus (CA1) and prelimbic cortex (PL), and tested the behavioral consequences at various stages of consolidation, acquisition and retrieval. Moreover, to test whether protein phosphatase regulates the effects of 5-aza, protein phosphatase (PP) 1/2A inhibitor okadaic acid (OA) was infused before 5-aza injection. We found that 5-aza injection into CA1 but not into PL significantly attenuated the consolidation and acquisition of mCPP, however, the inhibition of DNA methylation in PL but not in CA1 enhanced the retrieval of mCPP. All these behavioral effects were absent when OA was infused before 5-aza injection. These findings suggest that 5-aza interfere opiate-related memory, and protein phosphatase plays an important role in this process. PMID:25139850

  8. Morphine Induces Redox-Based Changes in Global DNA Methylation and Retrotransposon Transcription by Inhibition of Excitatory Amino Acid Transporter Type 3–Mediated Cysteine Uptake

    PubMed Central

    Trivedi, Malav; Shah, Jayni; Hodgson, Nathaniel; Byun, Hyang-Min

    2014-01-01

    Canonically, opioids influence cells by binding to a G protein–coupled opioid receptor, initiating intracellular signaling cascades, such as protein kinase, phosphatidylinositol 3-kinase, and extracellular receptor kinase pathways. This results in several downstream effects, including decreased levels of the reduced form of glutathione (GSH) and elevated oxidative stress, as well as epigenetic changes, especially in retrotransposons and heterochromatin, although the mechanism and consequences of these actions are unclear. We characterized the acute and long-term influence of morphine on redox and methylation status (including DNA methylation levels) in cultured neuronal SH-SY5Y cells. Acting via μ-opioid receptors, morphine inhibits excitatory amino acid transporter type 3–mediated cysteine uptake via multiple signaling pathways, involving different G proteins and protein kinases in a temporal manner. Decreased cysteine uptake was associated with decreases in both the redox and methylation status of neuronal cells, as defined by the ratios of GSH to oxidized forms of glutathione and S-adenosylmethionine to S-adenosylhomocysteine levels, respectively. Further, morphine induced global DNA methylation changes, including CpG sites in long interspersed nuclear elements (LINE-1) retrotransposons, resulting in increased LINE-1 mRNA. Together, these findings illuminate the mechanism by which morphine, and potentially other opioids, can influence neuronal-cell redox and methylation status including DNA methylation. Since epigenetic changes are implicated in drug addiction and tolerance phenomenon, this study could potentially extrapolate to elucidate a novel mechanism of action for other drugs of abuse. PMID:24569088

  9. Does reward unpredictability reflect risk?

    PubMed

    Anselme, Patrick

    2015-03-01

    Most decisions made in real-life situations are risky because they are associated with possible negative consequences. Current models of decision-making postulate that the occasional, unpredictable absence of reward that may result from free choice is a negative consequence interpreted as risk by organisms in laboratory situations. I argue that such a view is difficult to justify because, in most experimental paradigms, reward omission does not represent a cost for the decision-maker. Risk only exists when unpredictability may cause a potential loss of own limited resources, whether energetic, social, financial, and so on. Thus, the experimental methodologies used to test humans and non-humans relative to risk-taking seem to be limited to studying the effects of reward uncertainty in the absence of true decision cost. This may have important implications for the conclusions that can be drawn with respect to the neurobehavioural determinants of risk-taking in real-life situations. PMID:25496783

  10. Chronic morphine induces up-regulation of the pro-apoptotic Fas receptor and down-regulation of the anti-apoptotic Bcl-2 oncoprotein in rat brain

    PubMed Central

    Boronat, M Assumpció; García-Fuster, M Julia; García-Sevilla, Jesús A

    2001-01-01

    This study was designed to assess the influence of activation and blockade of the endogenous opioid system in the brain on two key proteins involved in the regulation of programmed cell death: the pro-apoptotic Fas receptor and the anti-apoptotic Bcl-2 oncoprotein. The acute treatment of rats with the μ-opioid receptor agonist morphine (3 – 30 mg kg−1, i.p., 2 h) did not modify the immunodensity of Fas or Bcl-2 proteins in the cerebral cortex. Similarly, the acute treatment with low and high doses of the antagonist naloxone (1 and 100 mg kg−1, i.p., 2 h) did not alter Fas or Bcl-2 protein expression in brain cortex. These results discounted a tonic regulation through opioid receptors on Fas and Bcl-2 proteins in rat brain. Chronic morphine (10 – 100 mg kg−1, 5 days, and 10 mg kg−1, 13 days) induced marked increases (47 – 123%) in the immunodensity of Fas receptor in the cerebral cortex. In contrast, chronic morphine (5 and 13 days) decreased the immunodensity of Bcl-2 protein (15 – 30%) in brain cortex. Chronic naloxone (10 mg kg−1, 13 days) did not alter the immunodensities of Fas and Bcl-2 proteins in the cerebral cortex. The concurrent chronic treatment (13 days) of naloxone (10 mg kg−1) and morphine (10 mg kg−1) completely prevented the morphine-induced increase in Fas receptor and decrease in Bcl-2 protein immunoreactivities in the cerebral cortex. The results indicate that morphine, through the sustained activation of opioid receptors, can promote abnormal programmed cell death by enhancing the expression of pro-apoptotic Fas receptor protein and damping the expression of anti-apoptotic Bcl-2 oncoprotein. PMID:11704646

  11. Attenuation of tolerance to opioid-induced antinociception and protection against morphine-induced decrease of neurofilament proteins by idazoxan and other I2-imidazoline ligands

    PubMed Central

    Boronat, M Assumpció; Olmos, Gabriel; García-Sevilla, Jesús A

    1998-01-01

    Agmatine, the proposed endogenous ligand for imidazoline receptors, has been shown to attenuate tolerance to morphine-induced antinociception (Kolesnikov et al., 1996). The main aim of this study was to assess if idazoxan, an α2-adrenoceptor antagonist that also interacts with imidazoline receptors, could also modulate opioid tolerance in rats and to establish which type of imidazoline receptors (or other receptors) are involved. Antinociceptive responses to opioid drugs were determined by the tail-flick test. The acute administration of morphine (10 mg kg−1, i.p., 30 min) or pentazocine (10 mg kg−1, i.p., 30 min) resulted in marked increases in tail-flick latencies (TFLs). As expected, the initial antinociceptive response to the opiates was lost after chronic (13 days) treatment (tolerance). When idazoxan (10 mg kg−1, i.p.) was given chronically 30 min before the opiates it completely prevented morphine tolerance and markedly attenuated tolerance to pentazocine (TFLs increased by 71–143% at day 13). Idazoxan alone did not modify TFLs. The concurrent chronic administration (10 mg kg−1, i.p., 13 days) of 2-BFI, LSL 60101, and LSL 61122 (valldemossine), selective and potent I2-imidazoline receptor ligands, and morphine (10 mg kg−1, i.p.), also prevented or attenuated morphine tolerance (TFLs increased by 64–172% at day 13). This attenuation of morphine tolerance was still apparent six days after discontinuation of the chronic treatment with LSL 60101-morphine. The acute treatment with these drugs did not potentiate morphine-induced antinociception. These drugs alone did not modify TFLs. Together, these results indicated the specific involvement of I2-imidazoline receptors in the modulation of opioid tolerance. The concurrent chronic (13 days) administration of RX821002 (10 mg kg−1, i.p.) and RS-15385-197 (1 mg kg−1, i.p.), selective α2-adrenoceptor antagonists, and morphine (10 mg kg−1, i.p.), did not

  12. Markov reward processes

    NASA Technical Reports Server (NTRS)

    Smith, R. M.

    1991-01-01

    Numerous applications in the area of computer system analysis can be effectively studied with Markov reward models. These models describe the behavior of the system with a continuous-time Markov chain, where a reward rate is associated with each state. In a reliability/availability model, upstates may have reward rate 1 and down states may have reward rate zero associated with them. In a queueing model, the number of jobs of certain type in a given state may be the reward rate attached to that state. In a combined model of performance and reliability, the reward rate of a state may be the computational capacity, or a related performance measure. Expected steady-state reward rate and expected instantaneous reward rate are clearly useful measures of the Markov reward model. More generally, the distribution of accumulated reward or time-averaged reward over a finite time interval may be determined from the solution of the Markov reward model. This information is of great practical significance in situations where the workload can be well characterized (deterministically, or by continuous functions e.g., distributions). The design process in the development of a computer system is an expensive and long term endeavor. For aerospace applications the reliability of the computer system is essential, as is the ability to complete critical workloads in a well defined real time interval. Consequently, effective modeling of such systems must take into account both performance and reliability. This fact motivates our use of Markov reward models to aid in the development and evaluation of fault tolerant computer systems.

  13. Reward Processing in Autism

    PubMed Central

    Scott-Van Zeeland, Ashley A.; Dapretto, Mirella; Ghahremani, Dara G.; Poldrack, Russell A.; Bookheimer, Susan Y.

    2011-01-01

    The social motivation hypothesis of autism posits that infants with autism do not experience social stimuli as rewarding, thereby leading to a cascade of potentially negative consequences for later development. While possible downstream effects of this hypothesis such as altered face and voice processing have been examined, there has not been a direct investigation of social reward processing in autism. Here we use functional magnetic resonance imaging to examine social and monetary rewarded implicit learning in children with and without autism spectrum disorders (ASD). Sixteen males with ASD and sixteen age- and IQ-matched typically developing (TD) males were scanned while performing two versions of a rewarded implicit learning task. In addition to examining responses to reward, we investigated the neural circuitry supporting rewarded learning and the relationship between these factors and social development. We found diminished neural responses to both social and monetary rewards in ASD, with a pronounced reduction in response to social rewards (SR). Children with ASD also demonstrated a further deficit in frontostriatal response during social, but not monetary, rewarded learning. Moreover, we show a relationship between ventral striatum activity and social reciprocity in TD children. Together, these data support the hypothesis that children with ASD have diminished neural responses to SR, and that this deficit relates to social learning impairments. PMID:20437601

  14. Rewarding effects of ethanol combined with low doses of morphine through dopamine D1 receptors.

    PubMed

    Ise, Yuya; Mori, Tomohisa; Katayama, Shirou; Nagase, Hiroshi; Suzuki, Tsutomu

    2013-01-01

    This study investigated whether ethanol combined with low doses of morphine produces rewarding effects in rats. Ethanol (0.075-1.2 g/kg, intraperitoneal [i.p.]) alone did not induce place preference. A moderate dose (1 mg/kg, s.c.), but not a low dose (0.1 mg/kg), of morphine induced a significant place preference. The combination of ethanol (0.075-0.6 g/kg, i.p.) and 0.1 mg/kg of morphine, as well as low doses of morphine (0.03-0.1 mg/kg, subcutaneous [s.c.]) combined with ethanol (0.3 g/kg, i.p.), induced a significant place preference. The combined effect of ethanol and morphine was significantly attenuated by naloxone (0.3 mg/kg, s.c.), naltrindole (1.0 mg/kg, s.c.), or long-term administration of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, s.c.). These results suggest that the rewarding effect induced by ethanol and a low dose of morphine is mediated by activation of the central opioidergic and dopaminergic systems through dopamine D1 receptors. PMID:23470804

  15. Rewarding the Resident Teacher

    ERIC Educational Resources Information Center

    McBride, Jennifer M.; Drake, Richard L.

    2011-01-01

    Residents routinely make significant contributions to the education of medical students. However, little attention has been paid to rewarding these individuals for their involvement in these academic activities. This report describes a program that rewards resident teachers with an academic appointment as a Clinical Instructor. The residents…

  16. Dopamine signaling in reward-related behaviors.

    PubMed

    Baik, Ja-Hyun

    2013-01-01

    Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors. PMID:24130517

  17. Opioids and sexual reward.

    PubMed

    Paredes, R G

    2014-06-01

    Various lines of research indicate that sexual reward is mediated by opioids in both males and females. In the first part I review basic ideas about sexual reward in humans followed by a description of what is known in rodents, where most of the studies have been done. Although a direct method to measure opioid release during mating is not yet available, there is a substantial amount of indirect evidence in humans and animals indicating that opioids are released during the execution of sexual behavior. Studies using the conditioned place preference (CPP) method where the effects of opioids upon sex induced reward have been evaluated will also be described. Evidence will also be presented indicating that the medial preoptic area (MPOA) plays a crucial role in the expression of opioid mediated sex-reward in males and females. This area is also important in other naturally occurring reward related behaviors such as singing. Opioids might be part of a system that mediates the rewarding properties of natural behaviors that are intrinsically rewarding. PMID:24239788

  18. Dopamine reward prediction error coding

    PubMed Central

    Schultz, Wolfram

    2016-01-01

    Reward prediction errors consist of the differences between received and predicted rewards. They are crucial for basic forms of learning about rewards and make us strive for more rewards—an evolutionary beneficial trait. Most dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error; they are activated by more reward than predicted (positive prediction error), remain at baseline activity for fully predicted rewards, and show depressed activity with less reward than predicted (negative prediction error). The dopamine signal increases nonlinearly with reward value and codes formal economic utility. Drugs of addiction generate, hijack, and amplify the dopamine reward signal and induce exaggerated, uncontrolled dopamine effects on neuronal plasticity. The striatum, amygdala, and frontal cortex also show reward prediction error coding, but only in subpopulations of neurons. Thus, the important concept of reward prediction errors is implemented in neuronal hardware. PMID:27069377

  19. Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring.

    PubMed

    Vassoler, Fair M; Wright, Siobhan J; Byrnes, Elizabeth M

    2016-04-01

    Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring. Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30-39) using an escalating dosing regimen. Animals then remained drug free until adulthood at which point they were mated with naïve males. Adult offspring (F1 animals) were tested for their response to morphine-induced (0, 1, 2.5, 5, and 10 mg/kg, s.c.) conditioned place preference (CPP) and context-independent morphine-induced sensitization. Naïve littermates were used to examine mu opiate receptor expression in the nucleus accumbens and ventral tegmental area. Results indicate that F1 females whose mothers were exposed to morphine during adolescence (Mor-F1) demonstrate significantly enhanced CPP to the lowest doses of morphine compared with Sal-F1 females. There were no differences in context-independent sensitization between maternal treatment groups. Protein expression analysis showed significantly increased levels of accumbal mu opiate receptor in Mor-F1 offspring and decreased levels in the VTA. Taken together, these findings demonstrate a shift in the dose response curve with regard to the rewarding effects of morphine in Mor-F1 females which may in part be due to altered mu opiate receptor expression in the nucleus accumbens and VTA. PMID:26700246

  20. Reward feedback accelerates motor learning.

    PubMed

    Nikooyan, Ali A; Ahmed, Alaa A

    2015-01-15

    Recent findings have demonstrated that reward feedback alone can drive motor learning. However, it is not yet clear whether reward feedback alone can lead to learning when a perturbation is introduced abruptly, or how a reward gradient can modulate learning. In this study, we provide reward feedback that decays continuously with increasing error. We asked whether it is possible to learn an abrupt visuomotor rotation by reward alone, and if the learning process could be modulated by combining reward and sensory feedback and/or by using different reward landscapes. We designed a novel visuomotor learning protocol during which subjects experienced an abruptly introduced rotational perturbation. Subjects received either visual feedback or reward feedback, or a combination of the two. Two different reward landscapes, where the reward decayed either linearly or cubically with distance from the target, were tested. Results demonstrate that it is possible to learn from reward feedback alone and that the combination of reward and sensory feedback accelerates learning. An analysis of the underlying mechanisms reveals that although reward feedback alone does not allow for sensorimotor remapping, it can nonetheless lead to broad generalization, highlighting a dissociation between remapping and generalization. Also, the combination of reward and sensory feedback accelerates learning without compromising sensorimotor remapping. These findings suggest that the use of reward feedback is a promising approach to either supplement or substitute sensory feedback in the development of improved neurorehabilitation techniques. More generally, they point to an important role played by reward in the motor learning process. PMID:25355957

  1. Orexin A-mediated AKT signaling in the dentate gyrus contributes to the acquisition, expression and reinstatement of morphine-induced conditioned place preference.

    PubMed

    Guo, Sui-Jun; Cui, Yu; Huang, Zhen-Zhen; Liu, Huan; Zhang, Xue-Qin; Jiang, Jin-Xiang; Xin, Wen-Jun

    2016-05-01

    Accumulating evidence indicates that the hippocampal dentate gyrus (DG), a critical brain region contributing to learning and memory, is involved in the addiction and relapse to abused drugs. Emerging studies also suggest the role of orexin signaling in the rewarding behavior induced by repeated exposure to opiates. In the present study, we investigated the dynamic adaptation of orexin signaling in the DG and its functional significance in the acquisition, expression, maintenance of and relapse to rewarding behavior induced by morphine. Repeated place conditioning with morphine significantly increased the orexin A content released from the lateral hypothalamic area projecting neurons into the DG. Local infusions of orexin A into the DG sensitized the acquisition of and relapse to the conditioned place preference induced by morphine. The application of the orexin receptor type 1 (OXR1) antagonist SB334867 significantly abolished the acquisition, expression and maintenance of the conditioned place preference induced by repeated exposure to morphine. Furthermore, the significant increase of the phosphorylation of AKT in the DG was associated with preference for the morphine-paired chamber in rats, which was reversed by the local administration of an OXR1 antagonist. Thus, these findings suggested that the dynamic upregulation of orexin A signaling, via the AKT pathway in the DG, may promote the acquisition and maintenance of opioid-induced craving behaviors and may increase sensitivity to the rewarding effect of subsequent opioids. PMID:25757577

  2. A Rewarding Partnership

    ERIC Educational Resources Information Center

    Abbott, Cheryl; Swanson, Marc

    2006-01-01

    A collaborating scientist--a rewarding addition to any high school science program--can help students collect and analyze data that either replicates or parallels the work of the partnering scientist. This type of partnership is beneficial for both students and scientists, and perhaps there has never been a better time to consider such a…

  3. The Rewards of Mentoring

    ERIC Educational Resources Information Center

    Green-Powell, Patricia

    2012-01-01

    A growing body of knowledge exists which describes the rewards and importance of mentors in the professional development of young men and women, particularly with relation to their interactions in professional and organizational settings. Research in both educational settings and the workplace indicates that students and employees alike are more…

  4. Do Economic Rewards Work?

    ERIC Educational Resources Information Center

    Wallace, Brian D.

    2009-01-01

    The love of learning--that intrinsic desire to gain knowledge and insight into new subjects--was once its own reward. That was altered decades ago when parents started using the proverbial "stick and carrot" to motivate their children to do well in school, or even just show up. Today, educators across the country have taken hold of this approach…

  5. Reward positivity: Reward prediction error or salience prediction error?

    PubMed

    Heydari, Sepideh; Holroyd, Clay B

    2016-08-01

    The reward positivity is a component of the human ERP elicited by feedback stimuli in trial-and-error learning and guessing tasks. A prominent theory holds that the reward positivity reflects a reward prediction error signal that is sensitive to outcome valence, being larger for unexpected positive events relative to unexpected negative events (Holroyd & Coles, 2002). Although the theory has found substantial empirical support, most of these studies have utilized either monetary or performance feedback to test the hypothesis. However, in apparent contradiction to the theory, a recent study found that unexpected physical punishments also elicit the reward positivity (Talmi, Atkinson, & El-Deredy, 2013). The authors of this report argued that the reward positivity reflects a salience prediction error rather than a reward prediction error. To investigate this finding further, in the present study participants navigated a virtual T maze and received feedback on each trial under two conditions. In a reward condition, the feedback indicated that they would either receive a monetary reward or not and in a punishment condition the feedback indicated that they would receive a small shock or not. We found that the feedback stimuli elicited a typical reward positivity in the reward condition and an apparently delayed reward positivity in the punishment condition. Importantly, this signal was more positive to the stimuli that predicted the omission of a possible punishment relative to stimuli that predicted a forthcoming punishment, which is inconsistent with the salience hypothesis. PMID:27184070

  6. Biological auctions with multiple rewards

    PubMed Central

    Reiter, Johannes G.; Kanodia, Ayush; Gupta, Raghav; Nowak, Martin A.; Chatterjee, Krishnendu

    2015-01-01

    The competition for resources among cells, individuals or species is a fundamental characteristic of evolution. Biological all-pay auctions have been used to model situations where multiple individuals compete for a single resource. However, in many situations multiple resources with various values exist and single reward auctions are not applicable. We generalize the model to multiple rewards and study the evolution of strategies. In biological all-pay auctions the bid of an individual corresponds to its strategy and is equivalent to its payment in the auction. The decreasingly ordered rewards are distributed according to the decreasingly ordered bids of the participating individuals. The reproductive success of an individual is proportional to its fitness given by the sum of the rewards won minus its payments. Hence, successful bidding strategies spread in the population. We find that the results for the multiple reward case are very different from the single reward case. While the mixed strategy equilibrium in the single reward case with more than two players consists of mostly low-bidding individuals, we show that the equilibrium can convert to many high-bidding individuals and a few low-bidding individuals in the multiple reward case. Some reward values lead to a specialization among the individuals where one subpopulation competes for the rewards and the other subpopulation largely avoids costly competitions. Whether the mixed strategy equilibrium is an evolutionarily stable strategy (ESS) depends on the specific values of the rewards. PMID:26180069

  7. Monetary rewards modulate inhibitory control.

    PubMed

    Herrera, Paula M; Speranza, Mario; Hampshire, Adam; Bekinschtein, Tristán A

    2014-01-01

    The ability to override a dominant response, often referred to as behavioral inhibition, is considered a key element of executive cognition. Poor behavioral inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioral inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/NoGo and Stop Signal Tasks (SSTs). Several studies have reported a positive modulatory effect of reward on performance in pathological conditions such as substance abuse, pathological gambling, and Attention Deficit Hyperactive Disorder (ADHD). However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory tasks are scarce and little is known about the finer grained relationship between motivation and inhibitory control. Here we probed the effect of reward magnitude and context on behavioral inhibition with three modified versions of the widely used SST. The pilot study compared inhibition performance during six blocks alternating neutral feedback, low, medium, and high monetary rewards. Study One compared increasing vs. decreasing rewards, with low, high rewards, and neutral feedback; whilst Study Two compared low and high reward magnitudes alone also in an increasing and decreasing reward design. The reward magnitude effect was not demonstrated in the pilot study, probably due to a learning effect induced by practice in this lengthy task. The reward effect per se was weak but the context (order of reward) was clearly suggested in Study One, and was particularly strongly confirmed in study two. In addition, these findings revealed a "kick start effect" over global performance measures. Specifically, there was a long lasting improvement in performance throughout the task when participants received the highest reward magnitudes at the beginning of the

  8. Monetary rewards modulate inhibitory control

    PubMed Central

    Herrera, Paula M.; Speranza, Mario; Hampshire, Adam; Bekinschtein, Tristán A.

    2014-01-01

    The ability to override a dominant response, often referred to as behavioral inhibition, is considered a key element of executive cognition. Poor behavioral inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioral inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/NoGo and Stop Signal Tasks (SSTs). Several studies have reported a positive modulatory effect of reward on performance in pathological conditions such as substance abuse, pathological gambling, and Attention Deficit Hyperactive Disorder (ADHD). However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory tasks are scarce and little is known about the finer grained relationship between motivation and inhibitory control. Here we probed the effect of reward magnitude and context on behavioral inhibition with three modified versions of the widely used SST. The pilot study compared inhibition performance during six blocks alternating neutral feedback, low, medium, and high monetary rewards. Study One compared increasing vs. decreasing rewards, with low, high rewards, and neutral feedback; whilst Study Two compared low and high reward magnitudes alone also in an increasing and decreasing reward design. The reward magnitude effect was not demonstrated in the pilot study, probably due to a learning effect induced by practice in this lengthy task. The reward effect per se was weak but the context (order of reward) was clearly suggested in Study One, and was particularly strongly confirmed in study two. In addition, these findings revealed a “kick start effect” over global performance measures. Specifically, there was a long lasting improvement in performance throughout the task when participants received the highest reward magnitudes at the beginning of the

  9. Endogenous opioids and reward.

    PubMed

    Van Ree, J M; Niesink, R J; Van Wolfswinkel, L; Ramsey, N F; Kornet, M M; Van Furth, W R; Vanderschuren, L J; Gerrits, M A; Van den Berg, C L

    2000-09-29

    The discovery of endogenous opioids has markedly influenced the research on the biology of addiction and reward brain processes. Evidence has been presented that these brain substances modulate brain stimulation reward, self-administration of different drugs of abuse, sexual behaviour and social behaviour. There appears to be two different domains in which endogenous opioids, present in separate and distinct brain regions, are involved. One is related to the modulation of incentive motivational processes and the other to the performance of certain behaviours. It is concluded that endogenous opioids may play a role in the vulnerability to certain diseases, such as addiction and autism, but also when the disease is present, such as alcoholism. PMID:11033317

  10. Critical role for the mediodorsal thalamus in permitting rapid reward-guided updating in stochastic reward environments.

    PubMed

    Chakraborty, Subhojit; Kolling, Nils; Walton, Mark E; Mitchell, Anna S

    2016-01-01

    Adaptive decision-making uses information gained when exploring alternative options to decide whether to update the current choice strategy. Magnocellular mediodorsal thalamus (MDmc) supports adaptive decision-making, but its causal contribution is not well understood. Monkeys with excitotoxic MDmc damage were tested on probabilistic three-choice decision-making tasks. They could learn and track the changing values in object-reward associations, but they were severely impaired at updating choices after reversals in reward contingencies or when there were multiple options associated with reward. These deficits were not caused by perseveration or insensitivity to negative feedback though. Instead, monkeys with MDmc lesions exhibited an inability to use reward to promote choice repetition after switching to an alternative option due to a diminished influence of recent past choices and the last outcome to guide future behavior. Together, these data suggest MDmc allows for the rapid discovery and persistence with rewarding options, particularly in uncertain or changing environments. PMID:27136677

  11. Social reward shapes attentional biases.

    PubMed

    Anderson, Brian A

    2016-01-01

    Paying attention to stimuli that predict a reward outcome is important for an organism to survive and thrive. When visual stimuli are associated with tangible, extrinsic rewards such as money or food, these stimuli acquire high attentional priority and come to automatically capture attention. In humans and other primates, however, many behaviors are not motivated directly by such extrinsic rewards, but rather by the social feedback that results from performing those behaviors. In the present study, I examine whether positive social feedback can similarly influence attentional bias. The results show that stimuli previously associated with a high probability of positive social feedback elicit value-driven attentional capture, much like stimuli associated with extrinsic rewards. Unlike with extrinsic rewards, however, such stimuli also influence task-specific motivation. My findings offer a potential mechanism by which social reward shapes the information that we prioritize when perceiving the world around us. PMID:25941868

  12. Mesolimbic recruitment by nondrug rewards in detoxified alcoholics: effort anticipation, reward anticipation and reward delivery

    PubMed Central

    Bjork, James M.; Smith, Ashley R.; Chen, Gang; Hommer, Daniel W.

    2011-01-01

    Aberrant sensitivity of incentive neurocircuitry to nondrug rewards has been suggested as either a risk factor for or consequence of drug addiction. Using functional magnetic resonance imaging, we tested whether alcohol-dependent patients (ADP: n = 29) showed altered recruitment of ventral striatal (VS) incentive neurocircuitry compared to controls (n = 23) by: 1) cues to respond for monetary rewards, 2) post-response anticipation of rewards, or 3) delivery of rewards. Using an instrumental task with two-stage presentation of reward-predictive information, subjects saw cues signaling opportunities to win $0, $1, or $10 for responding to a target. Following this response, subjects were notified whether their success would be indicated by a lexical notification (“Hit?”) or by delivery of a monetary reward (“Win?”). After a variable interval, subjects then viewed the trial outcome. We found no significant group differences in voxelwise activation by task contrasts, or in signal change extracted from VS. Both ADP and controls showed significant VS and other limbic recruitment by pre-response reward anticipation. In addition, controls also showed VS recruitment by post-response reward-anticipation, and ADP had appreciable subthreshold VS activation. Both groups also showed similar mesolimbic responses to reward deliveries. Across all subjects, a questionnaire measure of “hot” impulsivity correlated with VS recruitment by post-response anticipation of low rewards and with VS recruitment by delivery of low rewards. These findings indicate that incentive-motivational processing of nondrug rewards is substantially maintained in recovering alcoholics, and that reward-elicited VS recruitment correlates more with individual differences in trait impulsivity irrespective of addiction. PMID:22281932

  13. Reward processing in anorexia nervosa.

    PubMed

    Keating, Charlotte; Tilbrook, Alan J; Rossell, Susan L; Enticott, Peter G; Fitzgerald, Paul B

    2012-04-01

    Individuals with anorexia nervosa (AN) demonstrate a relentless engagement in behaviors aimed to reduce their weight, which leads to severe underweight status, and occasionally death. Neurobiological abnormalities, as a consequence of starvation are controversial: evidence, however, demonstrates abnormalities in the reward system of patients, and recovered individuals. Despite this, a unifying explanation for reward abnormalities observed in AN and their relevance to symptoms of the illness, remains incompletely understood. Theories explaining reward dysfunction have conventionally focused on anhedonia, describing that patients have an impaired ability to experience reward or pleasure. We review taste reward literature and propose that patients' reduced responses to conventional taste-reward tasks may reflect a fear of weight gain associated with the caloric nature of the tasks, rather than an impaired ability to experience reward. Consistent with this, we propose that patients are capable of 'liking' hedonic taste stimuli (e.g., identifying them), however, they do not 'want' or feel motivated for the stimuli in the same way that healthy controls report. Recent brain imaging data on more complex reward processing tasks provide insights into fronto-striatal neural circuit dysfunction related to altered reward processing in AN that challenges the relevance of anhedonia in explaining reward dysfunction in AN. In this way, altered activity of the anterior cingulate cortex and striatum could explain patients' pathological engagement in behaviors they consider rewarding (e.g., self-starvation) that are otherwise aversive or punishing, to those without the eating disorder. Such evidence for altered patterns of brain activity associated with reward processing tasks in patients and recovered individuals may provide important information about mechanisms underlying symptoms of AN, their future investigation, and the development of treatment approaches. PMID:22349445

  14. Affective neuroscience of pleasure: reward in humans and animals

    PubMed Central

    2010-01-01

    Introduction Pleasure and reward are generated by brain circuits that are largely shared between humans and other animals. Discussion Here, we survey some fundamental topics regarding pleasure mechanisms and explicitly compare humans and animals. Conclusion Topics surveyed include liking, wanting, and learning components of reward; brain coding versus brain causing of reward; subjective pleasure versus objective hedonic reactions; roles of orbitofrontal cortex and related cortex regions; subcortical hedonic hotspots for pleasure generation; reappraisals of dopamine and pleasure-electrode controversies; and the relation of pleasure to happiness. PMID:18311558

  15. Reward processing in adolescent rodents

    PubMed Central

    Simon, Nicholas W; Moghaddam, Bita

    2015-01-01

    Immaturities in adolescent reward processing are thought to contribute to poor decision making and increased susceptibility to develop addictive and psychiatric disorders. Very little is known; however, about how the adolescent brain processes reward. The current mechanistic theories of reward processing are derived from adult models. Here we review recent research focused on understanding of how the adolescent brain responds to rewards and reward-associated events. A critical aspect of this work is that age-related differences are evident in neuronal processing of reward-related events across multiple brain regions even when adolescent rats demonstrate behavior similar to adults. These include differences in reward processing between adolescent and adult rats in orbitofrontal cortex and dorsal striatum. Surprisingly, minimal age related differences are observed in ventral striatum, which has been a focal point of developmental studies. We go on to discuss the implications of these differences for behavioral traits affected in adolescence, such as impulsivity, risk-taking, and behavioral flexibility. Collectively, this work suggests that reward-evoked neural activity differs as a function of age and that regions such as the dorsal striatum that are not traditionally associated with affective processing in adults may be critical for reward processing and psychiatric vulnerability in adolescents. PMID:25524828

  16. Reward and the serotonergic system.

    PubMed

    Kranz, G S; Kasper, S; Lanzenberger, R

    2010-04-14

    Anhedonia, as a failure to experience rewarding stimuli, is a key characteristic of many psychiatric disorders including depression and schizophrenia. Investigations on the neurobiological correlates of reward and hedonia/anhedonia have been a growing subject of research demonstrating several neuromodulators to mediate different aspects of reward processing. Whereas the majority of research on reward mainly focused on the dopamine and opioid systems, a serotonergic mechanism has been neglected. However, recent promising results strengthen the pivotal role of serotonin in reward processing. Evidence includes electrophysical and pharmacological as well as genetic and imaging studies. Primate research using single-unit recording of neurons within the dorsal raphe nucleus argues for a serotonergic mediation of reward value, whereas studies using intracranial self-stimulation point to an important contribution of serotonin in modulating motivational aspects of rewarding brain stimulation. Pharmacological studies using agonists and antagonists of serotonergic receptor subtypes and approaches investigating an increase or decrease of the extracellular level of serotonin offer strong evidence for a serotonergic mediation, ranging from aversion to pleasure. This review provides an argument for serotonin as a fundamental mediator of emotional, motivational and cognitive aspects of reward representation, which makes it possibly as important as dopamine for reward processing. PMID:20109531

  17. Monetary rewards influence retrieval orientations.

    PubMed

    Halsband, Teresa M; Ferdinand, Nicola K; Bridger, Emma K; Mecklinger, Axel

    2012-09-01

    Reward anticipation during learning is known to support memory formation, but its role in retrieval processes is so far unclear. Retrieval orientations, as a reflection of controlled retrieval processing, are one aspect of retrieval that might be modulated by reward. These processes can be measured using the event-related potentials (ERPs) elicited by retrieval cues from tasks with different retrieval requirements, such as via changes in the class of targeted memory information. To determine whether retrieval orientations of this kind are modulated by reward during learning, we investigated the effects of high and low reward expectancy on the ERP correlates of retrieval orientation in two separate experiments. The reward manipulation at study in Experiment 1 was associated with later memory performance, whereas in Experiment 2, reward was directly linked to accuracy in the study task. In both studies, the participants encoded mixed lists of pictures and words preceded by high- or low-reward cues. After 24 h, they performed a recognition memory exclusion task, with words as the test items. In addition to a previously reported material-specific effect of retrieval orientation, a frontally distributed, reward-associated retrieval orientation effect was found in both experiments. These findings suggest that reward motivation during learning leads to the adoption of a reward-associated retrieval orientation to support the retrieval of highly motivational information. Thus, ERP retrieval orientation effects not only reflect retrieval processes related to the sought-for materials, but also relate to the reward conditions with which items were combined during encoding. PMID:22547161

  18. Reward Modulates Adaptations to Conflict

    ERIC Educational Resources Information Center

    Braem, Senne; Verguts, Tom; Roggeman, Chantal; Notebaert, Wim

    2012-01-01

    Both cognitive conflict (e.g. Verguts & Notebaert, 2009) and reward signals (e.g. Waszak & Pholulamdeth, 2009) have been proposed to enhance task-relevant associations. Bringing these two notions together, we predicted that reward modulates conflict-based sequential adaptations in cognitive control. This was tested combining either a single…

  19. Reward deficiency and anti-reward in pain chronification.

    PubMed

    Borsook, D; Linnman, C; Faria, V; Strassman, A M; Becerra, L; Elman, I

    2016-09-01

    Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification). PMID:27246519

  20. Adaptive Reward Pursuit: How Effort Requirements Affect Unconscious Reward Responses and Conscious Reward Decisions

    ERIC Educational Resources Information Center

    Bijleveld, Erik; Custers, Ruud; Aarts, Henk

    2012-01-01

    When in pursuit of rewards, humans weigh the value of potential rewards against the amount of effort that is required to attain them. Although previous research has generally conceptualized this process as a deliberate calculation, recent work suggests that rudimentary mechanisms--operating without conscious intervention--play an important role as…

  1. Reward-Guided Learning with and without Causal Attribution

    PubMed Central

    Jocham, Gerhard; Brodersen, Kay H.; Constantinescu, Alexandra O.; Kahn, Martin C.; Ianni, Angela M.; Walton, Mark E.; Rushworth, Matthew F.S.; Behrens, Timothy E.J.

    2016-01-01

    Summary When an organism receives a reward, it is crucial to know which of many candidate actions caused this reward. However, recent work suggests that learning is possible even when this most fundamental assumption is not met. We used novel reward-guided learning paradigms in two fMRI studies to show that humans deploy separable learning mechanisms that operate in parallel. While behavior was dominated by precise contingent learning, it also revealed hallmarks of noncontingent learning strategies. These learning mechanisms were separable behaviorally and neurally. Lateral orbitofrontal cortex supported contingent learning and reflected contingencies between outcomes and their causal choices. Amygdala responses around reward times related to statistical patterns of learning. Time-based heuristic mechanisms were related to activity in sensorimotor corticostriatal circuitry. Our data point to the existence of several learning mechanisms in the human brain, of which only one relies on applying known rules about the causal structure of the task. PMID:26971947

  2. Reward-Guided Learning with and without Causal Attribution.

    PubMed

    Jocham, Gerhard; Brodersen, Kay H; Constantinescu, Alexandra O; Kahn, Martin C; Ianni, Angela M; Walton, Mark E; Rushworth, Matthew F S; Behrens, Timothy E J

    2016-04-01

    When an organism receives a reward, it is crucial to know which of many candidate actions caused this reward. However, recent work suggests that learning is possible even when this most fundamental assumption is not met. We used novel reward-guided learning paradigms in two fMRI studies to show that humans deploy separable learning mechanisms that operate in parallel. While behavior was dominated by precise contingent learning, it also revealed hallmarks of noncontingent learning strategies. These learning mechanisms were separable behaviorally and neurally. Lateral orbitofrontal cortex supported contingent learning and reflected contingencies between outcomes and their causal choices. Amygdala responses around reward times related to statistical patterns of learning. Time-based heuristic mechanisms were related to activity in sensorimotor corticostriatal circuitry. Our data point to the existence of several learning mechanisms in the human brain, of which only one relies on applying known rules about the causal structure of the task. PMID:26971947

  3. Timing in reward and decision processes

    PubMed Central

    Bermudez, Maria A.; Schultz, Wolfram

    2014-01-01

    Sensitivity to time, including the time of reward, guides the behaviour of all organisms. Recent research suggests that all major reward structures of the brain process the time of reward occurrence, including midbrain dopamine neurons, striatum, frontal cortex and amygdala. Neuronal reward responses in dopamine neurons, striatum and frontal cortex show temporal discounting of reward value. The prediction error signal of dopamine neurons includes the predicted time of rewards. Neurons in the striatum, frontal cortex and amygdala show responses to reward delivery and activities anticipating rewards that are sensitive to the predicted time of reward and the instantaneous reward probability. Together these data suggest that internal timing processes have several well characterized effects on neuronal reward processing. PMID:24446502

  4. Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward.

    PubMed

    Macoveanu, Julian; Henningsson, Susanne; Pinborg, Anja; Jensen, Peter; Knudsen, Gitte M; Frokjaer, Vibe G; Siebner, Hartwig R

    2016-03-01

    Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex-steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women. PMID:26245498

  5. Peripheral signals modifying food reward.

    PubMed

    Menzies, John R W; Skibicka, Karolina P; Egecioglu, Emil; Leng, Gareth; Dickson, Suzanne L

    2012-01-01

    The pleasure derived from eating may feel like a simple emotion, but the decision to eat, and perhaps more importantly what to eat, involves central pathways linking energy homeostasis and reward and their regulation by metabolic and endocrine factors. Evidence is mounting that modulation of the hedonic aspects of energy balance is under the control of peripheral neuropeptides conventionally associated with homeostatic appetite control. Here, we describe the significance of reward in feeding, the neural substrates underlying the reward pathway and their modification by peptides released into the circulation from peripheral tissues. PMID:22249813

  6. Dopamine: the rewarding years

    PubMed Central

    Marsden, Charles A

    2006-01-01

    Dopamine has moved from being an insignificant intermediary in the formation of noradrenaline in 1957 to its present-day position as a major neurotransmitter in the brain. This neurotransmitter is involved in the control of movement and Parkinson's disease, the neurobiology and symptoms of schizophrenia and attention deficit hyperactivity disorder. It is also considered an essential element in the brain reward system and in the action of many drugs of abuse. This evolution reflects the ability of several famous names in neuropharmacology, neurology and psychiatry to apply new techniques to ask and answer the right questions. There is now excellent knowledge about the metabolism of dopamine, dopamine receptor systems and the structural organisation of dopamine pathways in the brain. Less is known about the function of the different receptors and how the various dopamine pathways are organised to produce normal behaviour, which exhibits disruption in the disease states mentioned. In particular, we have very limited information as to why and how the dopamine system dies or becomes abnormal in Parkinson's disease or a neurodevelopmental disorder such as schizophrenia. Dopamine neurones account for less than 1% of the total neuronal population of the brain, but have a profound effect on function. The future challenge is to understand how dopamine is involved in the integration of information to produce a relevant response rather than to study dopamine in isolation from other transmission systems. This integrated approach should lead to greater understanding and improved treatment of diseases involving dopamine. PMID:16402097

  7. Rewarding the Gifted Art Teacher.

    ERIC Educational Resources Information Center

    Hurwitz, Al

    1983-01-01

    A program to reward exceptional art teachers, sponsored by the Chroma Acrylics Corporation, is described. Application procedures, conditions, award winners, and the projects they plan with the award money are covered. (IS)

  8. Reward functions of the basal ganglia.

    PubMed

    Schultz, Wolfram

    2016-07-01

    Besides their fundamental movement function evidenced by Parkinsonian deficits, the basal ganglia are involved in processing closely linked non-motor, cognitive and reward information. This review describes the reward functions of three brain structures that are major components of the basal ganglia or are closely associated with the basal ganglia, namely midbrain dopamine neurons, pedunculopontine nucleus, and striatum (caudate nucleus, putamen, nucleus accumbens). Rewards are involved in learning (positive reinforcement), approach behavior, economic choices and positive emotions. The response of dopamine neurons to rewards consists of an early detection component and a subsequent reward component that reflects a prediction error in economic utility, but is unrelated to movement. Dopamine activations to non-rewarded or aversive stimuli reflect physical impact, but not punishment. Neurons in pedunculopontine nucleus project their axons to dopamine neurons and process sensory stimuli, movements and rewards and reward-predicting stimuli without coding outright reward prediction errors. Neurons in striatum, besides their pronounced movement relationships, process rewards irrespective of sensory and motor aspects, integrate reward information into movement activity, code the reward value of individual actions, change their reward-related activity during learning, and code own reward in social situations depending on whose action produces the reward. These data demonstrate a variety of well-characterized reward processes in specific basal ganglia nuclei consistent with an important function in non-motor aspects of motivated behavior. PMID:26838982

  9. Premotor and Motor Cortices Encode Reward

    PubMed Central

    Ramkumar, Pavan; Dekleva, Brian; Cooler, Sam; Miller, Lee; Kording, Konrad

    2016-01-01

    Rewards associated with actions are critical for motivation and learning about the consequences of one’s actions on the world. The motor cortices are involved in planning and executing movements, but it is unclear whether they encode reward over and above limb kinematics and dynamics. Here, we report a categorical reward signal in dorsal premotor (PMd) and primary motor (M1) neurons that corresponds to an increase in firing rates when a trial was not rewarded regardless of whether or not a reward was expected. We show that this signal is unrelated to error magnitude, reward prediction error, or other task confounds such as reward consumption, return reach plan, or kinematic differences across rewarded and unrewarded trials. The availability of reward information in motor cortex is crucial for theories of reward-based learning and motivational influences on actions. PMID:27564707

  10. Premotor and Motor Cortices Encode Reward.

    PubMed

    Ramkumar, Pavan; Dekleva, Brian; Cooler, Sam; Miller, Lee; Kording, Konrad

    2016-01-01

    Rewards associated with actions are critical for motivation and learning about the consequences of one's actions on the world. The motor cortices are involved in planning and executing movements, but it is unclear whether they encode reward over and above limb kinematics and dynamics. Here, we report a categorical reward signal in dorsal premotor (PMd) and primary motor (M1) neurons that corresponds to an increase in firing rates when a trial was not rewarded regardless of whether or not a reward was expected. We show that this signal is unrelated to error magnitude, reward prediction error, or other task confounds such as reward consumption, return reach plan, or kinematic differences across rewarded and unrewarded trials. The availability of reward information in motor cortex is crucial for theories of reward-based learning and motivational influences on actions. PMID:27564707

  11. Complex effects of reward upshift on consummatory behavior.

    PubMed

    Annicchiarico, Ivan; Glueck, Amanda C; Cuenya, Lucas; Kawasaki, Katsuyoshi; Conrad, Shannon E; Papini, Mauricio R

    2016-08-01

    Exposing rats to an upshift from a small reward to a larger reward sometimes yields evidence of consummatory successive positive contrast (cSPC), an effect that could be a suitable animal model of positive emotion. However, cSPC is an unreliable effect. Ten experiments explored the effects of an upshift in sucrose or saccharin concentration on consummatory behavior under several conditions. There was occasional evidence of cSPC, but mostly a combination of increased consummatory behavior relative to preshift reward concentrations and a reduced behavioral level relative to unshifted controls. Such a pattern is consistent with processes causing opposite changes on behavior. Reward upshift may induce processes that suppress behavior, such as taste neophobia (induced by an intense sucrose taste) and generalization decrement (induced by novelty in reward conditions after the upshift). An experiment tested the role of such novelty-related effects by preexposing animals to either the upshift concentration (12% sucrose) or water during three days before the start of the experiment. Sucrose-preexposed animals drank significantly more than water-preexposed animals during the upshift, but just as much as unshifted controls (i.e., no evidence of cSPC). These results suggest that cSPC may be difficult to obtain reliably because reward upshift induces opposing processes. However, they also seriously question the ontological status of cSPC. PMID:27298234

  12. Co-activation of μ- and δ-opioid receptors elicits tolerance to morphine-induced ventilatory depression via generation of peroxynitrite.

    PubMed

    Young, Alex P; Gruber, Ryan B; Discala, Joe F; May, Walter J; McLaughlin, Dylan; Palmer, Lisa A; Lewis, Stephen J

    2013-05-01

    We determined whether pretreatment with (1) the μ-/δ-opioid receptor (μ-/δ-OR) antagonist, naloxone, (2) the δ1,2-OR antagonist, naltrindole, or (3) the peroxynitrite scavenger, d-penicillamine, affects the development of tolerance to the ventilatory depressant effects of morphine in rats. The injection of morphine in vehicle-pretreated rats decreased minute ventilation predominantly via decreases in tidal volume. Pretreatment with naloxone blunted the responses to morphine whereas pretreatment with naltrindole or d-penicillamine did not. A second injection of morphine, given one day later, elicited markedly smaller responses in vehicle rats whereas it elicited pronounced ventilatory depression in rats that were pretreated with naloxone, naltrindole or d-penicillamine (prior to morphine) the day before. Moreover, the ventilatory responses elicited by subsequent exposure to a hypoxic-hypercapnic challenge were markedly depressed in naloxone- or d-penicillamine-pretreated rats compared to vehicle-pretreated rats. These findings suggest that activation of μ- and δ-ORs causes tolerance to the ventilatory depressant effects of morphine at least partly via the generation of peroxynitrite. PMID:23473921

  13. The evolution of anti-social rewarding and its countermeasures in public goods games.

    PubMed

    dos Santos, Miguel

    2015-01-01

    Cooperation in joint enterprises can easily break down when self-interests are in conflict with collective benefits, causing a tragedy of the commons. In such social dilemmas, the possibility for contributors to invest in a common pool-rewards fund, which will be shared exclusively among contributors, can be powerful for averting the tragedy, as long as the second-order dilemma (i.e. withdrawing contribution to reward funds) can be overcome (e.g. with second-order sanctions). However, the present paper reveals the vulnerability of such pool-rewarding mechanisms to the presence of reward funds raised by defectors and shared among them (i.e. anti-social rewarding), as it causes a cooperation breakdown, even when second-order sanctions are possible. I demonstrate that escaping this social trap requires the additional condition that coalitions of defectors fare poorly compared with pro-socials, with either (i) better rewarding abilities for the latter or (ii) reward funds that are contingent upon the public good produced beforehand, allowing groups of contributors to invest more in reward funds than groups of defectors. These results suggest that the establishment of cooperation through a collective positive incentive mechanism is highly vulnerable to anti-social rewarding and requires additional countermeasures to act in combination with second-order sanctions. PMID:25429015

  14. The evolution of anti-social rewarding and its countermeasures in public goods games

    PubMed Central

    dos Santos, Miguel

    2015-01-01

    Cooperation in joint enterprises can easily break down when self-interests are in conflict with collective benefits, causing a tragedy of the commons. In such social dilemmas, the possibility for contributors to invest in a common pool-rewards fund, which will be shared exclusively among contributors, can be powerful for averting the tragedy, as long as the second-order dilemma (i.e. withdrawing contribution to reward funds) can be overcome (e.g. with second-order sanctions). However, the present paper reveals the vulnerability of such pool-rewarding mechanisms to the presence of reward funds raised by defectors and shared among them (i.e. anti-social rewarding), as it causes a cooperation breakdown, even when second-order sanctions are possible. I demonstrate that escaping this social trap requires the additional condition that coalitions of defectors fare poorly compared with pro-socials, with either (i) better rewarding abilities for the latter or (ii) reward funds that are contingent upon the public good produced beforehand, allowing groups of contributors to invest more in reward funds than groups of defectors. These results suggest that the establishment of cooperation through a collective positive incentive mechanism is highly vulnerable to anti-social rewarding and requires additional countermeasures to act in combination with second-order sanctions. PMID:25429015

  15. Microglia disrupt mesolimbic reward circuitry in chronic pain.

    PubMed

    Taylor, Anna M W; Castonguay, Annie; Taylor, Alison J; Murphy, Niall P; Ghogha, Atefeh; Cook, Christopher; Xue, Lihua; Olmstead, Mary C; De Koninck, Yves; Evans, Christopher J; Cahill, Catherine M

    2015-06-01

    Chronic pain attenuates midbrain dopamine (DA) transmission, as evidenced by a decrease in opioid-evoked DA release in the ventral striatum, suggesting that the occurrence of chronic pain impairs reward-related behaviors. However, mechanisms by which pain modifies DA transmission remain elusive. Using in vivo microdialysis and microinjection of drugs into the mesolimbic DA system, we demonstrate in mice and rats that microglial activation in the VTA compromises not only opioid-evoked release of DA, but also other DA-stimulating drugs, such as cocaine. Our data show that loss of stimulated extracellular DA is due to impaired chloride homeostasis in midbrain GABAergic interneurons. Treatment with minocycline or interfering with BDNF signaling restored chloride transport within these neurons and recovered DA-dependent reward behavior. Our findings demonstrate that a peripheral nerve injury causes activated microglia within reward circuitry that result in disruption of dopaminergic signaling and reward behavior. These results have broad implications that are not restricted to the problem of pain, but are also relevant to affective disorders associated with disruption of reward circuitry. Because chronic pain causes glial activation in areas of the CNS important for mood and affect, our findings may translate to other disorders, including anxiety and depression, that demonstrate high comorbidity with chronic pain. PMID:26041913

  16. Rewarding imperfect motor performance reduces adaptive changes.

    PubMed

    van der Kooij, K; Overvliet, K E

    2016-06-01

    Could a pat on the back affect motor adaptation? Recent studies indeed suggest that rewards can boost motor adaptation. However, the rewards used were typically reward gradients that carried quite detailed information about performance. We investigated whether simple binary rewards affected how participants learned to correct for a visual rotation of performance feedback in a 3D pointing task. To do so, we asked participants to align their unseen hand with virtual target cubes in alternating blocks with and without spatial performance feedback. Forty participants were assigned to one of two groups: a 'spatial only' group, in which the feedback consisted of showing the (perturbed) endpoint of the hand, or to a 'spatial & reward' group, in which a reward could be received in addition to the spatial feedback. In addition, six participants were tested in a 'reward only' group. Binary reward was given when the participants' hand landed in a virtual 'hit area' that was adapted to individual performance to reward about half the trials. The results show a typical pattern of adaptation in both the 'spatial only' and the 'spatial & reward' groups, whereas the 'reward only' group was unable to adapt. The rewards did not affect the overall pattern of adaptation in the 'spatial & reward' group. However, on a trial-by-trial basis, the rewards reduced adaptive changes to spatial errors. PMID:26758721

  17. Evolutionary advantages of adaptive rewarding

    NASA Astrophysics Data System (ADS)

    Szolnoki, Attila; Perc, Matjaž

    2012-09-01

    Our well-being depends on both our personal success and the success of our society. The realization of this fact makes cooperation an essential trait. Experiments have shown that rewards can elevate our readiness to cooperate, but since giving a reward inevitably entails paying a cost for it, the emergence and stability of such behavior remains elusive. Here we show that allowing for the act of rewarding to self-organize in dependence on the success of cooperation creates several evolutionary advantages that instill new ways through which collaborative efforts are promoted. Ranging from indirect territorial battle to the spontaneous emergence and destruction of coexistence, phase diagrams and the underlying spatial patterns reveal fascinatingly rich social dynamics that explain why this costly behavior has evolved and persevered. Comparisons with adaptive punishment, however, uncover an Achilles heel of adaptive rewarding, coming from over-aggression, which in turn hinders optimal utilization of network reciprocity. This may explain why, despite its success, rewarding is not as firmly embedded into our societal organization as punishment.

  18. Introduction: Addiction and Brain Reward and Anti-Reward Pathways

    PubMed Central

    Gardner, Eliot L.

    2013-01-01

    Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly) and that they enhance the functioning of the reward circuitry of the brain (producing the “high” that the drug-user seeks). The core reward circuitry consists of an “in series” circuit linking the ventral tegmental area, nucleus accumbens, and ventral pallidum - via the medial forebrain bundle. Although originally believed to encode simply the set-point of hedonic tone, these circuits are now believed to be functionally far more complex - also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. “Hedonic dysregulation” within these circuits may lead to addiction. The “second-stage” dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component. All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dopaminergic reward synaptic function in the nucleus accumbens. Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level). For some classes of addictive drugs (e.g., opiates), tolerance to the euphoric effects develops with chronic use. Post-use dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get “high,” but simply to get back to normal (“get straight”). The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically, and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse. There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction. In short, the

  19. Academic Rewards in Higher Education.

    ERIC Educational Resources Information Center

    Lewis, Darrel R., Ed.; Becker, William E., Jr., Ed.

    A colloquium series in higher education at the University of Minnesota in the fall and winter of 1977-1978 examined the influence of academic reward systems on faculty behavior and academic productivity. These essays are the collective results of their findings and recommendations. Essays include: "Perspectives from Psychology: Financial…

  20. Virtual Rewards for Driving Green

    ERIC Educational Resources Information Center

    Pritchard, Josh

    2010-01-01

    Carbon dioxide from automobiles is a major contributor to global climate change. In "Virtual Rewards for Driving Green," Josh Pritchard proposes a computer application that will enable fuel-efficient drivers to earn "green" dollars with which to buy digital merchandise on the Web. Can getting items that exist only in cyberspace actually change a…

  1. Addiction: Beyond dopamine reward circuitry

    SciTech Connect

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.

    2011-09-13

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  2. The Hidden Costs of Rewards.

    ERIC Educational Resources Information Center

    Deci, Edward L.

    1976-01-01

    This paper discusses ways managers can motivate their employees to work and at the same time to increase their performance. Two theories of motivation--Vroom's theory and Atkinson's theory--focus on the use of extrinsic and intrinsic rewards respectively. A managerial strategy that combines the best of both intrinsic and extrinsic approaches to…

  3. Reward, Distraction, and the Overjustification Effect

    ERIC Educational Resources Information Center

    Smith, Timothy W.; Pittman, Thane S.

    1978-01-01

    This study tests two differing hypotheses: the competing response hypothesis, which states that both reward and non-reward distractions produce decreases in interest which weaken over repeated trials, and the attribution/overjustification hypothesis, which maintains that rewards produce a decrease in interest that does not weaken over trials.…

  4. Critical role for the mediodorsal thalamus in permitting rapid reward-guided updating in stochastic reward environments

    PubMed Central

    Chakraborty, Subhojit; Kolling, Nils; Walton, Mark E; Mitchell, Anna S

    2016-01-01

    Adaptive decision-making uses information gained when exploring alternative options to decide whether to update the current choice strategy. Magnocellular mediodorsal thalamus (MDmc) supports adaptive decision-making, but its causal contribution is not well understood. Monkeys with excitotoxic MDmc damage were tested on probabilistic three-choice decision-making tasks. They could learn and track the changing values in object-reward associations, but they were severely impaired at updating choices after reversals in reward contingencies or when there were multiple options associated with reward. These deficits were not caused by perseveration or insensitivity to negative feedback though. Instead, monkeys with MDmc lesions exhibited an inability to use reward to promote choice repetition after switching to an alternative option due to a diminished influence of recent past choices and the last outcome to guide future behavior. Together, these data suggest MDmc allows for the rapid discovery and persistence with rewarding options, particularly in uncertain or changing environments. DOI: http://dx.doi.org/10.7554/eLife.13588.001 PMID:27136677

  5. Reward-associated stimuli capture the eyes in spite of strategic attentional set.

    PubMed

    Hickey, Clayton; van Zoest, Wieske

    2013-11-01

    Theories of reinforcement learning have proposed that the association of reward to visual stimuli may cause these objects to become fundamentally salient and thus attention-drawing. A number of recent studies have investigated the oculomotor correlates of this reward-priming effect, but there is some ambiguity in this literature regarding the involvement of top-down attentional set. Existing paradigms tend to create a situation where participants are actively looking for a reward-associated stimulus before subsequently showing that this selective bias sustains when it no longer has strategic purpose. This perseveration of attentional set is potentially different in nature than the direct impact of reward proposed by theory. Here we investigate the effect of reward on saccadic selection in a paradigm where strategic attentional set is decoupled from the effect of reward. We find that during search for a uniquely oriented target, the receipt of reward following selection of a target characterized by an irrelevant unique color causes subsequent stimuli characterized by this color to be preferentially selected. Importantly, this occurs regardless of whether the color characterizes the target or distractor. Other analyses demonstrate that only features associated with correct selection of the target prime the target representation, and that the magnitude of this effect can be predicted by variability in saccadic indices of feedback processing. These results add to a growing literature demonstrating that reward guides visual selection, often in spite of our strategic efforts otherwise. PMID:24084197

  6. Balancing risk and reward: a rat model of risky decision making.

    PubMed

    Simon, Nicholas W; Gilbert, Ryan J; Mayse, Jeffrey D; Bizon, Jennifer L; Setlow, Barry

    2009-09-01

    We developed a behavioral task in rats to assess the influence of risk of punishment on decision making. Male Long-Evans rats were given choices between pressing a lever to obtain a small, 'safe' food reward and a large food reward associated with risk of punishment (footshock). Each test session consisted of 5 blocks of 10 choice trials, with punishment risk increasing with each consecutive block (0, 25, 50, 75, 100%). Preference for the large, 'risky' reward declined with both increased probability and increased magnitude of punishment, and reward choice was not affected by the level of satiation or the order of risk presentation. Performance in this risky decision-making task was correlated with the degree to which the rats discounted the value of probabilistic rewards, but not delayed rewards. Finally, the acute effects of different doses of amphetamine and cocaine on risky decision making were assessed. Systemic amphetamine administration caused a dose-dependent decrease in choice of the large risky reward (ie, it made rats more risk averse). Cocaine did not cause a shift in reward choice, but instead impaired the rats' sensitivity to changes in punishment risk. These results should prove useful for investigating neuropsychiatric disorders in which risk taking is a prominent feature, such as attention deficit/hyperactivity disorder and addiction. PMID:19440192

  7. Incremental effects of reward on creativity.

    PubMed

    Eisenberger, R; Rhoades, L

    2001-10-01

    The authors examined 2 ways reward might increase creativity. First, reward contingent on creativity might increase extrinsic motivation. Studies 1 and 2 found that repeatedly giving preadolescent students reward for creative performance in 1 task increased their creativity in subsequent tasks. Study 3 reported that reward promised for creativity increased college students' creative task performance. Second, expected reward for high performance might increase creativity by enhancing perceived self-determination and, therefore, intrinsic task interest. Study 4 found that employees' intrinsic job interest mediated a positive relationship between expected reward for high performance and creative suggestions offered at work. Study 5 found that employees' perceived self-determination mediated a positive relationship between expected reward for high performance and the creativity of anonymous suggestions for helping the organization. PMID:11642357

  8. Brain Circuits Encoding Reward from Pain Relief.

    PubMed

    Navratilova, Edita; Atcherley, Christopher W; Porreca, Frank

    2015-11-01

    Relief from pain in humans is rewarding and pleasurable. Primary rewards, or reward-predictive cues, are encoded in brain reward/motivational circuits. While considerable advances have been made in our understanding of reward circuits underlying positive reinforcement, less is known about the circuits underlying the hedonic and reinforcing actions of pain relief. We review findings from electrophysiological, neuroimaging, and behavioral studies supporting the concept that the rewarding effect of pain relief requires opioid signaling in the anterior cingulate cortex (ACC), activation of midbrain dopamine neurons, and the release of dopamine in the nucleus accumbens (NAc). Understanding of circuits that govern the reward of pain relief may allow the discovery of more effective and satisfying therapies for patients with acute or chronic pain. PMID:26603560

  9. When unconscious rewards boost cognitive task performance inefficiently: the role of consciousness in integrating value and attainability information

    PubMed Central

    Zedelius, Claire M.; Veling, Harm; Aarts, Henk

    2012-01-01

    Research has shown that high vs. low value rewards improve cognitive task performance independent of whether they are perceived consciously or unconsciously. However, efficient performance in response to high value rewards also depends on whether or not rewards are attainable. This raises the question of whether unconscious reward processing enables people to take into account such attainability information. Building on a theoretical framework according to which conscious reward processing is required to enable higher level cognitive processing, the present research tested the hypothesis that conscious but not unconscious reward processing enables integration of reward value with attainability information. In two behavioral experiments, participants were exposed to mask high and low value coins serving as rewards on a working memory (WM) task. The likelihood for conscious processing was manipulated by presenting the coins relatively briefly (17 ms) or long and clearly visible (300 ms). Crucially, rewards were expected to be attainable or unattainable. Requirements to integrate reward value with attainability information varied across experiments. Results showed that when integration of value and attainability was required (Experiment 1), long reward presentation led to efficient performance, i.e., selectively improved performance for high value attainable rewards. In contrast, in the short presentation condition, performance was increased for high value rewards even when these were unattainable. This difference between the effects of long and short presentation time disappeared when integration of value and attainability information was not required (Experiment 2). Together these findings suggest that unconsciously processed reward information is not integrated with attainability expectancies, causing inefficient effort investment. These findings are discussed in terms of a unique role of consciousness in efficient allocation of effort to cognitive control

  10. Evaluating the neurobiology of sexual reward.

    PubMed

    Paredes, Raúl G

    2009-01-01

    There is much evidence that naturally occurring behaviors (e.g., the ingestion of food and water) and social behaviors (e.g., play, maternal behavior) can induce a reward state. This review includes definitions to distinguish between "reward" and "reinforcement," and a description of methods to assess reward and demonstrate that social interactions can indeed produce a positive affective (PA) state. Operant responses, partner preference, and sexual incentive motivation are all effective methods for evaluating approach behaviors under different conditions. The method most frequently used to evaluate a positive affective or reward state is conditioned place preference (CPP), which entails modification of an animal's initial preference after alternating exposure to a control stimulus in one chamber and a rewarding condition in the other. At the end of the training the animal shows a clear preference for the compartment associated with the rewarding stimulus. CPP demonstrates that it is possible to use different treatments and naturally occurring behaviors (e.g., water or food consumption, exercise) to induce a reward state. Sexual interactions and other social behaviors also produce a clear change of preference, indicating the induction of a reward or PA state. The reward state in males and females is mediated by opioids, and the medial preoptic area of the anterior hypothalamus is a crucial site for sexual reward. PMID:19106449

  11. Inflated reward value in early opiate withdrawal.

    PubMed

    Wassum, Kate M; Greenfield, Venuz Y; Linker, Kay E; Maidment, Nigel T; Ostlund, Sean B

    2016-03-01

    Through incentive learning, the emotional experience of a reward in a relevant need state (e.g. hunger for food) sets the incentive value that guides the performance of actions that earn that reward when the need state is encountered again. Opiate withdrawal has been proposed as a need state in which, through experience, opiate value can be increased, resulting in escalated opiate self-administration. Endogenous opioid transmission plays anatomically dissociable roles in the positive emotional experience of reward consumption and incentive learning. We, therefore, sought to determine if chronic opiate exposure and withdrawal produces a disruption in the fundamental incentive learning process such that reward seeking, even for non-opiate rewards, can become maladaptive, inconsistent with the emotional experience of reward consumption and irrespective of need. Rats trained to earn sucrose or water on a reward-seeking chain were treated with morphine (10-30 mg/kg, s.c.) daily for 11 days prior to testing in withdrawal. Opiate-withdrawn rats showed elevated reward-seeking actions, but only after they experienced the reward in withdrawal, an effect that was strongest in early (1-3 days), as opposed to late (14-16 days), withdrawal. This was sufficient to overcome a negative reward value change induced by sucrose experience in satiety and, in certain circumstances, was inconsistent with the emotional experience of reward consumption. Lastly, we found that early opiate withdrawal-induced inflation of reward value was blocked by inactivation of basolateral amygdala mu opioid receptors. These data suggest that in early opiate withdrawal, the incentive learning process is disrupted, resulting in maladaptive reward seeking. PMID:25081350

  12. Cueing task goals and earning money: Relatively high monetary rewards reduce failures to act on goals in a Stroop task

    PubMed Central

    Aarts, Henk

    2010-01-01

    We examined the role of monetary rewards in failures to act on goals in a Stroop task. Based on recent developments in theorizing on the interplay between rewards and cognitive control, we hypothesized that relatively high monetary rewards enhance the focus and stability of a cued task goal compared to low monetary rewards, and hence cause a reduction in failures to act on current task goals under circumstances that warrant top–down goal implementation. To test this, participants received a modified version of the Stroop task, in which they were either briefly cued with the goal of naming the color or meaning of targets on a trial-by-trial basis. After goal cuing, but before presenting the target, either a low or high reward cue was presented. Results showed that higher rewards produced a general speed-up. More importantly, Stroop interference on error rates was lower in the high reward condition compared to the low reward condition, revealing that the rewards enhanced focus and stability of the cued goal. These results provide support for theorizing that reward processing modulates utility assessment of current goals by affecting attention to facilitate goal-directed behavior. PMID:20651907

  13. Cueing task goals and earning money: Relatively high monetary rewards reduce failures to act on goals in a Stroop task.

    PubMed

    Veling, Harm; Aarts, Henk

    2010-06-01

    We examined the role of monetary rewards in failures to act on goals in a Stroop task. Based on recent developments in theorizing on the interplay between rewards and cognitive control, we hypothesized that relatively high monetary rewards enhance the focus and stability of a cued task goal compared to low monetary rewards, and hence cause a reduction in failures to act on current task goals under circumstances that warrant top-down goal implementation. To test this, participants received a modified version of the Stroop task, in which they were either briefly cued with the goal of naming the color or meaning of targets on a trial-by-trial basis. After goal cuing, but before presenting the target, either a low or high reward cue was presented. Results showed that higher rewards produced a general speed-up. More importantly, Stroop interference on error rates was lower in the high reward condition compared to the low reward condition, revealing that the rewards enhanced focus and stability of the cued goal. These results provide support for theorizing that reward processing modulates utility assessment of current goals by affecting attention to facilitate goal-directed behavior. PMID:20651907

  14. Sensitivity to Temporal Reward Structure in Amygdala Neurons

    PubMed Central

    Bermudez, Maria A.; Göbel, Carl; Schultz, Wolfram

    2012-01-01

    Summary The time of reward and the temporal structure of reward occurrence fundamentally influence behavioral reinforcement and decision processes [1–11]. However, despite knowledge about timing in sensory and motor systems [12–17], we know little about temporal mechanisms of neuronal reward processing. In this experiment, visual stimuli predicted different instantaneous probabilities of reward occurrence that resulted in specific temporal reward structures. Licking behavior demonstrated that the animals had developed expectations for the time of reward that reflected the instantaneous reward probabilities. Neurons in the amygdala, a major component of the brain's reward system [18–29], showed two types of reward signal, both of which were sensitive to the expected time of reward. First, the time courses of anticipatory activity preceding reward delivery followed the specific instantaneous reward probabilities and thus paralleled the temporal reward structures. Second, the magnitudes of responses following reward delivery covaried with the instantaneous reward probabilities, reflecting the influence of temporal reward structures at the moment of reward delivery. In being sensitive to temporal reward structure, the reward signals of amygdala neurons reflected the temporally specific expectations of reward. The data demonstrate an active involvement of amygdala neurons in timing processes that are crucial for reward function. PMID:22959346

  15. Reward magnitude effects on temporal discrimination

    PubMed Central

    Galtress, Tiffany; Kirkpatrick, Kimberly

    2016-01-01

    Changes in reward magnitude or value have been reported to produce effects on timing behavior, which have been attributed to changes in the speed of an internal pacemaker in some instances and to attentional factors in other cases. The present experiments therefore aimed to clarify the effects of reward magnitude on timing processes. In Experiment 1, rats were trained to discriminate a short (2 s) vs. a long (8 s) signal followed by testing with intermediate durations. Then, the reward on short or long trials was increased from 1 to 4 pellets in separate groups. Experiment 2 measured the effect of different reward magnitudes associated with the short vs. long signals throughout training. Finally, Experiment 3 controlled for satiety effects during the reward magnitude manipulation phase. A general flattening of the psychophysical function was evident in all three experiments, suggesting that unequal reward magnitudes may disrupt attention to duration.

  16. Reward magnitude effects on temporal discrimination

    PubMed Central

    Galtress, Tiffany; Kirkpatrick, Kimberly

    2014-01-01

    Changes in reward magnitude or value have been reported to produce effects on timing behavior, which have been attributed to changes in the speed of an internal pacemaker in some instances and to attentional factors in other cases. The present experiments therefore aimed to clarify the effects of reward magnitude on timing processes. In Experiment 1, rats were trained to discriminate a short (2 s) vs. a long (8 s) signal followed by testing with intermediate durations. Then, the reward on short or long trials was increased from 1 to 4 pellets in separate groups. Experiment 2 measured the effect of different reward magnitudes associated with the short vs. long signals throughout training. Finally, Experiment 3 controlled for satiety effects during the reward magnitude manipulation phase. A general flattening of the psychophysical function was evident in all three experiments, suggesting that unequal reward magnitudes may disrupt attention to duration. PMID:24965705

  17. Learning Reward Uncertainty in the Basal Ganglia.

    PubMed

    Mikhael, John G; Bogacz, Rafal

    2016-09-01

    Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid) options with variable reward can be controlled by increasing (or decreasing) the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions. PMID:27589489

  18. D1- and D2-like dopamine receptors in the CA1 region of the hippocampus are involved in the acquisition and reinstatement of morphine-induced conditioned place preference.

    PubMed

    Assar, Nasim; Mahmoudi, Dorna; Farhoudian, Ali; Farhadi, Mohammad Hasan; Fatahi, Zahra; Haghparast, Abbas

    2016-10-01

    The hippocampus plays a vital role in processing contextual memories and reward related learning tasks, such as conditioned place preference (CPP). Among the neurotransmitters in the hippocampus, dopamine is deeply involved in reward-related processes. This study assessed the role of D1- and D2-like dopamine receptors within the CA1 region of the hippocampus in the acquisition and reinstatement of morphine-CPP. To investigate the role of D1 and D2 receptors in morphine acquisition, the animals received different doses of D1- and/or D2-like dopamine receptor antagonists (SCH23390 and sulpiride, respectively) into the CA1, 5min before the administration of morphine (5mg/kg, subcutaneously) during a 3-days conditioning phase. To evaluate the involvement of these receptors in morphine reinstatement, the animals received different doses of SCH23390 or sulpiride (after extinction period) 5min before the administration of a low dose of morphine (1mg/kg) in order to reinstate the extinguished morphine-CPP. Conditioning scores were recorded by Ethovision software. The results of this study showed that the administration of SCH23390 or sulpiride, significantly decreased the acquisition of morphine-CPP. Besides, the injection of these antagonists before the administration of a priming dose of morphine, following the extinction period, decreased the reinstatement of morphine-CPP in sacrificed rats. However, the effect of sulpiride on the acquisition and reinstatement of morphine-CPP was more significant than that of SCH23390. These findings suggested that D1- and D2-like dopamine receptors in the CA1 are involved in the acquisition and reinstatement of morphine-CPP, and antagonism of these receptors can reduce the rewarding properties of morphine. PMID:27374160

  19. Attention-deficit-hyperactivity disorder and reward deficiency syndrome

    PubMed Central

    Blum, Kenneth; Chen, Amanda Lih-Chuan; Braverman, Eric R; Comings, David E; Chen, Thomas JH; Arcuri, Vanessa; Blum, Seth H; Downs, Bernard W; Waite, Roger L; Notaro, Alison; Lubar, Joel; Williams, Lonna; Prihoda, Thomas J; Palomo, Tomas; Oscar-Berman, Marlene

    2008-01-01

    Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the “brain reward cascade,” especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD2 A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other “reward genes” are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions. PMID:19183781

  20. Reward-dependent modulation of movement variability.

    PubMed

    Pekny, Sarah E; Izawa, Jun; Shadmehr, Reza

    2015-03-01

    Movement variability is often considered an unwanted byproduct of a noisy nervous system. However, variability can signal a form of implicit exploration, indicating that the nervous system is intentionally varying the motor commands in search of actions that yield the greatest success. Here, we investigated the role of the human basal ganglia in controlling reward-dependent motor variability as measured by trial-to-trial changes in performance during a reaching task. We designed an experiment in which the only performance feedback was success or failure and quantified how reach variability was modulated as a function of the probability of reward. In healthy controls, reach variability increased as the probability of reward decreased. Control of variability depended on the history of past rewards, with the largest trial-to-trial changes occurring immediately after an unrewarded trial. In contrast, in participants with Parkinson's disease, a known example of basal ganglia dysfunction, reward was a poor modulator of variability; that is, the patients showed an impaired ability to increase variability in response to decreases in the probability of reward. This was despite the fact that, after rewarded trials, reach variability in the patients was comparable to healthy controls. In summary, we found that movement variability is partially a form of exploration driven by the recent history of rewards. When the function of the human basal ganglia is compromised, the reward-dependent control of movement variability is impaired, particularly affecting the ability to increase variability after unsuccessful outcomes. PMID:25740529

  1. Adolescents and Androgens, Receptors and Rewards

    PubMed Central

    Sato, Satoru M.; Schulz, Kalynn M.; Sisk, Cheryl L.; Wood, Ruth I.

    2008-01-01

    Adolescence is associated with increases in pleasure-seeking behaviors, which, in turn, are shaped by the pubertal activation of the hypothalamo-pituitary-gonadal axis. In animal models of naturally rewarding behaviors, such as sex, testicular androgens contribute to the development and expression of the behavior in males. To effect behavioral maturation, the brain undergoes significant remodeling during adolescence, and many of the changes are likewise sensitive to androgens, presumably acting through androgen receptors (AR). Given the delicate interaction of gonadal hormones and brain development, it is no surprise that disruption of hormone levels during this sensitive period significantly alters adolescent and adult behaviors. In male hamsters, exposure to testosterone during adolescence is required for normal expression of adult sexual behavior. Males deprived of androgens during puberty display sustained deficits in mating. Conversely, androgens alone are not sufficient to induce mating in prepubertal males, even though brain AR are present before puberty. In this context, wide-spread use of anabolic-androgenic steroids (AAS) during adolescence is a significant concern. AAS abuse has the potential to alter both the timing and the levels of androgens in adolescent males. In hamsters, adolescent AAS exposure increases aggression, and causes lasting changes in neurotransmitter systems. In addition, AAS are themselves reinforcing, as demonstrated by self-administration of testosterone and other AAS. However, recent evidence suggests that the reinforcing effects of androgens may not require classical AR. Therefore, further examination of interactions between androgens and rewarding behaviors in the adolescent brain is required for a better understanding of AAS abuse. PMID:18343381

  2. Reward and non-reward learning of flower colours in the butterfly Byasa alcinous (Lepidoptera: Papilionidae)

    NASA Astrophysics Data System (ADS)

    Kandori, Ikuo; Yamaki, Takafumi

    2012-09-01

    Learning plays an important role in food acquisition for a wide range of insects. To increase their foraging efficiency, flower-visiting insects may learn to associate floral cues with the presence (so-called reward learning) or the absence (so-called non-reward learning) of a reward. Reward learning whilst foraging for flowers has been demonstrated in many insect taxa, whilst non-reward learning in flower-visiting insects has been demonstrated only in honeybees, bumblebees and hawkmoths. This study examined both reward and non-reward learning abilities in the butterfly Byasa alcinous whilst foraging among artificial flowers of different colours. This butterfly showed both types of learning, although butterflies of both sexes learned faster via reward learning. In addition, females learned via reward learning faster than males. To the best of our knowledge, these are the first empirical data on the learning speed of both reward and non-reward learning in insects. We discuss the adaptive significance of a lower learning speed for non-reward learning when foraging on flowers.

  3. Cognitive processing of food rewards.

    PubMed

    Higgs, Suzanne

    2016-09-01

    Cues associated with tasty foods, such as their smell or taste, are strong motivators of eating, but the power of food cues on behaviour varies from moment to moment and from person to person. Variation in the rewarding value of a food with metabolic state explains why food cues are more attractive when hungry. However, cognitive processes are also important determinants of our responses to food cues. An urge to consume a tempting food may be resisted if, for example, a person has a longer term goal of weight loss. There is also evidence that responses to food cues can be facilitated or inhibited by memory processes. The aim of this review is to add to the literature on cognitive control of eating by reviewing recent evidence on the influence of working memory and episodic memory processes on responses to food cues. It is argued that processing of food information in working memory affects how much attention is paid to food cues in the environment and promotes the motivation to seek out food in the absence of direct contact with food cues. It is further argued that memories of specific recent eating episodes play an important role in directing food choices and influencing when and how much we eat. However, these memory processes are prone to disruption. When this happens, eating behaviour may become more cue-driven and less flexible. In the modern food environment, disruption of cognitive processing of food reward cues may lead to overconsumption and obesity. PMID:26458961

  4. Mechanisms of habitual approach: Failure to suppress irrelevant responses evoked by previously reward-associated stimuli.

    PubMed

    Anderson, Brian A; Folk, Charles L; Garrison, Rebecca; Rogers, Leeland

    2016-06-01

    Reward learning has a powerful influence on the attention system, causing previously reward-associated stimuli to automatically capture attention. Difficulty ignoring stimuli associated with drug reward has been linked to addiction relapse, and the attention system of drug-dependent patients seems especially influenced by reward history. This and other evidence suggests that value-driven attention has consequences for behavior and decision-making, facilitating a bias to approach and consume the previously reward-associated stimulus even when doing so runs counter to current goals and priorities. Yet, a mechanism linking value-driven attention to behavioral responding and a general approach bias is lacking. Here we show that previously reward-associated stimuli escape inhibitory processing in a go/no-go task. Control experiments confirmed that this value-dependent failure of goal-directed inhibition could not be explained by search history or residual motivation, but depended specifically on the learned association between particular stimuli and reward outcome. When a previously high-value stimulus is encountered, the response codes generated by that stimulus are automatically afforded high priority, bypassing goal-directed cognitive processes involved in suppressing task-irrelevant behavior. (PsycINFO Database Record PMID:27054684

  5. Statistical Mechanics of the Delayed Reward-Based Learning with Node Perturbation

    NASA Astrophysics Data System (ADS)

    Hiroshi Saito,; Kentaro Katahira,; Kazuo Okanoya,; Masato Okada,

    2010-06-01

    In reward-based learning, reward is typically given with some delay after a behavior that causes the reward. In machine learning literature, the framework of the eligibility trace has been used as one of the solutions to handle the delayed reward in reinforcement learning. In recent studies, the eligibility trace is implied to be important for difficult neuroscience problem known as the “distal reward problem”. Node perturbation is one of the stochastic gradient methods from among many kinds of reinforcement learning implementations, and it searches the approximate gradient by introducing perturbation to a network. Since the stochastic gradient method does not require a objective function differential, it is expected to be able to account for the learning mechanism of a complex system, like a brain. We study the node perturbation with the eligibility trace as a specific example of delayed reward-based learning, and analyzed it using a statistical mechanics approach. As a result, we show the optimal time constant of the eligibility trace respect to the reward delay and the existence of unlearnable parameter configurations.

  6. Performance-Based Rewards and Work Stress

    ERIC Educational Resources Information Center

    Ganster, Daniel C.; Kiersch, Christa E.; Marsh, Rachel E.; Bowen, Angela

    2011-01-01

    Even though reward systems play a central role in the management of organizations, their impact on stress and the well-being of workers is not well understood. We review the literature linking performance-based reward systems to various indicators of employee stress and well-being. Well-controlled experiments in field settings suggest that certain…

  7. Social Reward Questionnaire (SRQ): development and validation.

    PubMed

    Foulkes, Lucy; Viding, Essi; McCrory, Eamon; Neumann, Craig S

    2014-01-01

    Human beings seek out social interactions as a source of reward. To date, there have been limited attempts to identify different forms of social reward, and little is known about how the value of social rewards might vary between individuals. This study aimed to address both these issues by developing the Social Reward Questionnaire (SRQ), a measure of individual differences in the value of different social rewards. Exploratory factor analysis (EFA) was run on an initial set of 75 items (N = 305). Based on this analysis, confirmatory factor analysis (CFA) was then conducted on a second sample (N = 505) with a refined 23-item scale. This analysis was used to test a six-factor structure, which resulted in good model fit (CFI = 0.96, RSMEA = 0.07). The factors represent six subscales of social reward defined as follows: Admiration; Negative Social Potency; Passivity; Prosocial Interactions; Sexual Reward; and Sociability. All subscales demonstrated good test-retest reliability and internal consistency. Each subscale also showed a distinct pattern of associations with external correlates measuring personality traits, attitudes, and goals, thus demonstrating construct validity. Taken together, the findings suggest that the SRQ is a reliable, valid measure that can be used to assess individual differences in the value experienced from different social rewards. PMID:24653711

  8. Social Reward Questionnaire (SRQ): development and validation

    PubMed Central

    Foulkes, Lucy; Viding, Essi; McCrory, Eamon; Neumann, Craig S.

    2014-01-01

    Human beings seek out social interactions as a source of reward. To date, there have been limited attempts to identify different forms of social reward, and little is known about how the value of social rewards might vary between individuals. This study aimed to address both these issues by developing the Social Reward Questionnaire (SRQ), a measure of individual differences in the value of different social rewards. Exploratory factor analysis (EFA) was run on an initial set of 75 items (N = 305). Based on this analysis, confirmatory factor analysis (CFA) was then conducted on a second sample (N = 505) with a refined 23-item scale. This analysis was used to test a six-factor structure, which resulted in good model fit (CFI = 0.96, RSMEA = 0.07). The factors represent six subscales of social reward defined as follows: Admiration; Negative Social Potency; Passivity; Prosocial Interactions; Sexual Reward; and Sociability. All subscales demonstrated good test-retest reliability and internal consistency. Each subscale also showed a distinct pattern of associations with external correlates measuring personality traits, attitudes, and goals, thus demonstrating construct validity. Taken together, the findings suggest that the SRQ is a reliable, valid measure that can be used to assess individual differences in the value experienced from different social rewards. PMID:24653711

  9. Video game training and the reward system.

    PubMed

    Lorenz, Robert C; Gleich, Tobias; Gallinat, Jürgen; Kühn, Simone

    2015-01-01

    Video games contain elaborate reinforcement and reward schedules that have the potential to maximize motivation. Neuroimaging studies suggest that video games might have an influence on the reward system. However, it is not clear whether reward-related properties represent a precondition, which biases an individual toward playing video games, or if these changes are the result of playing video games. Therefore, we conducted a longitudinal study to explore reward-related functional predictors in relation to video gaming experience as well as functional changes in the brain in response to video game training. Fifty healthy participants were randomly assigned to a video game training (TG) or control group (CG). Before and after training/control period, functional magnetic resonance imaging (fMRI) was conducted using a non-video game related reward task. At pretest, both groups showed strongest activation in ventral striatum (VS) during reward anticipation. At posttest, the TG showed very similar VS activity compared to pretest. In the CG, the VS activity was significantly attenuated. This longitudinal study revealed that video game training may preserve reward responsiveness in the VS in a retest situation over time. We suggest that video games are able to keep striatal responses to reward flexible, a mechanism which might be of critical value for applications such as therapeutic cognitive training. PMID:25698962

  10. Video game training and the reward system

    PubMed Central

    Lorenz, Robert C.; Gleich, Tobias; Gallinat, Jürgen; Kühn, Simone

    2015-01-01

    Video games contain elaborate reinforcement and reward schedules that have the potential to maximize motivation. Neuroimaging studies suggest that video games might have an influence on the reward system. However, it is not clear whether reward-related properties represent a precondition, which biases an individual toward playing video games, or if these changes are the result of playing video games. Therefore, we conducted a longitudinal study to explore reward-related functional predictors in relation to video gaming experience as well as functional changes in the brain in response to video game training. Fifty healthy participants were randomly assigned to a video game training (TG) or control group (CG). Before and after training/control period, functional magnetic resonance imaging (fMRI) was conducted using a non-video game related reward task. At pretest, both groups showed strongest activation in ventral striatum (VS) during reward anticipation. At posttest, the TG showed very similar VS activity compared to pretest. In the CG, the VS activity was significantly attenuated. This longitudinal study revealed that video game training may preserve reward responsiveness in the VS in a retest situation over time. We suggest that video games are able to keep striatal responses to reward flexible, a mechanism which might be of critical value for applications such as therapeutic cognitive training. PMID:25698962

  11. Reward Magnitude Effects on Temporal Discrimination

    ERIC Educational Resources Information Center

    Galtress, Tiffany; Kirkpatrick, Kimberly

    2010-01-01

    Changes in reward magnitude or value have been reported to produce effects on timing behavior, which have been attributed to changes in the speed of an internal pacemaker in some instances and to attentional factors in other cases. The present experiments therefore aimed to clarify the effects of reward magnitude on timing processes. In Experiment…

  12. Reward modulates perception in binocular rivalry.

    PubMed

    Marx, Svenja; Einhäuser, Wolfgang

    2015-01-01

    Our perception does not provide us with an exact imprint of the outside world, but is continuously adapted to our internal expectations, task sets, and behavioral goals. Although effects of reward-or value in general-on perception therefore seem likely, how valuation modulates perception and how such modulation relates to attention is largely unknown. We probed effects of reward on perception by using a binocular-rivalry paradigm. Distinct gratings drifting in opposite directions were presented to each observer's eyes. To objectify their subjective perceptual experience, the optokinetic nystagmus was used as measure of current perceptual dominance. In a first experiment, one of the percepts was either rewarded or attended. We found that reward and attention similarly biased perception. In a second experiment, observers performed an attentionally demanding task either on the rewarded stimulus, the other stimulus, or both. We found that-on top of an attentional effect on perception-at each level of attentional load, reward still modulated perception by increasing the dominance of the rewarded percept. Similarly, penalizing one percept increased dominance of the other at each level of attentional load. In turn, rewarding-and similarly nonpunishing-a percept yielded performance benefits that are typically associated with selective attention. In conclusion, our data show that value modulates perception in a similar way as the volitional deployment of attention, even though the relative effect of value is largely unaffected by an attention task. PMID:25589295

  13. Reward eliminates retrieval-induced forgetting

    PubMed Central

    Imai, Hisato; Kim, Dongho; Sasaki, Yuka; Watanabe, Takeo

    2014-01-01

    Although it is well known that reward enhances learning and memory, how extensively such enhancement occurs remains unclear. To address this question, we examined how reward influences retrieval-induced forgetting (RIF) in which the retrieval of a nonpracticed item under the same category as a practiced item is worse than the retrieval of a nonpracticed item outside the category. Subjects were asked to try to encode category-exemplar pairs (e.g., FISH–salmon). Then, they were presented with a category name and a two-letter word stem (e.g., FISH–sa) and were asked to complete an encoded word (retrieval practice). For a correct response, apple juice was given as a reward in the reward condition and a beeping sound was presented in the no-reward condition. Finally, subjects were asked to report whether each exemplar had been presented in the first phase. RIF was replicated in the no-reward condition. However, in the reward condition, RIF was eliminated. These results suggest that reward enhances processing of retrieval of unpracticed members by mechanisms such as spreading activation within the same category, irrespective of whether items were practiced or not. PMID:25404297

  14. The Recognition and Reward of Employee Performance.

    ERIC Educational Resources Information Center

    Bishop, John

    A study compared different firms' methods of recognizing and rewarding employee performance and examined the impact of such recognition and reward on such factors as involuntary and voluntary labor turnover and worker productivity. Data from a survey of 3,412 employers that was sponsored by the National Institute of Education and the National…

  15. Course Budgeting: Balancing Rewards and Risks.

    ERIC Educational Resources Information Center

    Matkin, Gary W.

    Continuing education programmers must be risk takers; however, they should not be gamblers. The most successful of them are able to estimate a balance between potential rewards and risks, taking chances when the odds are favorable. Although it is essential that course planners balance potential financial rewards and risks, it is important to bear…

  16. Adolescent Depression: Stress and Reward Dysfunction

    PubMed Central

    Auerbach, Randy P.; Admon, Roee; Pizzagalli, Diego A.

    2014-01-01

    Adolescence is a peak period for the onset of depression, and it is also a time marked by substantial stress as well as neural development within the brain reward circuitry. In the current review, we provide a selective overview of current animal and human research investigating the relationship among reward processes, stress, and depression. Three separate, but related, etiological models examine the differential roles that stress may play with regard to reward dysfunction and adolescent depression. First, the reward mediation model suggests that acute and chronic stress contribute to reward deficits, which in turn, potentiate depressive symptoms and/or increase the risk for depression. Second, in line with the stress generation perspective, it is plausible that premorbid reward-related dysfunction generates stress, in particular interpersonal stress, which then leads to the manifestation of depressive symptoms. Last, consistent with a diathesis-stress model, the interaction between stress and premorbid reward dysfunction may contribute to the onset of depression. Given the equifinal nature of depression, these models could shed important light on different etiological pathways during adolescence, particularly as they may relate to understanding the heterogeneity of depression. To highlight the translational potential of these insights, a hypothetical case study is provided as means of demonstrating the importance of targeting reward dysfunction in both assessment and treatment of adolescent depression. PMID:24704785

  17. A new perspective on human reward research: how consciously and unconsciously perceived reward information influences performance.

    PubMed

    Zedelius, Claire M; Veling, Harm; Custers, Ruud; Bijleveld, Erik; Chiew, Kimberly S; Aarts, Henk

    2014-06-01

    The question of how human performance can be improved through rewards is a recurrent topic of interest in psychology and neuroscience. Traditional, cognitive approaches to this topic have focused solely on consciously communicated rewards. Recently, a largely neuroscience-inspired perspective has emerged to examine the potential role of conscious awareness of reward information in effective reward pursuit. The present article reviews research employing a newly developed monetary-reward-priming paradigm that allows for a systematic investigation of this perspective. We analyze this research to identify similarities and differences in how consciously and unconsciously perceived rewards impact three distinct aspects relevant to performance: decision making, task preparation, and task execution. We further discuss whether conscious awareness, in modulating the effects of reward information, plays a role similar to its role in modulating the effects of other affective information. Implications of these insights for understanding the role of consciousness in modulating goal-directed behavior more generally are discussed. PMID:24399682

  18. Discrete coding of stimulus value, reward expectation, and reward prediction error in the dorsal striatum.

    PubMed

    Oyama, Kei; Tateyama, Yukina; Hernádi, István; Tobler, Philippe N; Iijima, Toshio; Tsutsui, Ken-Ichiro

    2015-11-01

    To investigate how the striatum integrates sensory information with reward information for behavioral guidance, we recorded single-unit activity in the dorsal striatum of head-fixed rats participating in a probabilistic Pavlovian conditioning task with auditory conditioned stimuli (CSs) in which reward probability was fixed for each CS but parametrically varied across CSs. We found that the activity of many neurons was linearly correlated with the reward probability indicated by the CSs. The recorded neurons could be classified according to their firing patterns into functional subtypes coding reward probability in different forms such as stimulus value, reward expectation, and reward prediction error. These results suggest that several functional subgroups of dorsal striatal neurons represent different kinds of information formed through extensive prior exposure to CS-reward contingencies. PMID:26378201

  19. Social reward among juvenile mice

    PubMed Central

    Panksepp, J B; Lahvis, G P

    2007-01-01

    Mammalian social relationships, such as mother–offspring attachments and pair bonds, can directly affect reproductive output. However, conspecifics approach one another in a comparatively broad range of contexts, so conceivably there are motivations for social congregation other than those underlying reproduction, parental care or territoriality. Here, we show that reward mediated by social contact is a fundamental aspect of juvenile mouse sociality. Employing a novel social conditioned place preference (SCPP) procedure, we demonstrate that social proximity is rewarding for juvenile mice from three inbred strains (A/J, C57BL/6J and DBA/2J), while mice from a fourth strain (BALB/cJ) are much less responsive to social contact. Importantly, this strain-dependent difference was not related to phenotypic variability in exploratory behavior or contextual learning nor influenced by the genetic background associated with maternal care or social conditioning. Furthermore, the SCPP phenotype was expressed early in development (postnatal day 25) and did not require a specific sex composition within the conditioning group. Finally, SCPP responses resulted from an interaction between two specifiable processes: one component of the interaction facilitated approach toward environments that were associated with social salience, whereas a second component mediated avoidance of environmental cues that predicted social isolation. We have thus identified a genetically prescribed process that can attribute value onto conditions predicting a general form of social contact. To our knowledge, this is the first definitive evidence to show that genetic variation can influence a form of social valuation not directly related to a reproductive behavior. PMID:17212648

  20. CLEANing the Reward: Counterfactual Actions to Remove Exploratory Action Noise in Multiagent Learning

    NASA Technical Reports Server (NTRS)

    HolmesParker, Chris; Taylor, Mathew E.; Tumer, Kagan; Agogino, Adrian

    2014-01-01

    Learning in multiagent systems can be slow because agents must learn both how to behave in a complex environment and how to account for the actions of other agents. The inability of an agent to distinguish between the true environmental dynamics and those caused by the stochastic exploratory actions of other agents creates noise in each agent's reward signal. This learning noise can have unforeseen and often undesirable effects on the resultant system performance. We define such noise as exploratory action noise, demonstrate the critical impact it can have on the learning process in multiagent settings, and introduce a reward structure to effectively remove such noise from each agent's reward signal. In particular, we introduce Coordinated Learning without Exploratory Action Noise (CLEAN) rewards and empirically demonstrate their benefits

  1. A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons

    PubMed Central

    Qi, Jia; Zhang, Shiliang; Wang, Hui-Ling; Wang, Huikun; de Jesus Aceves Buendia, Jose; Hoffman, Alexander F.; Lupica, Carl R.; Seal, Rebecca P.; Morales, Marisela

    2014-01-01

    Electrical stimulation of the dorsal raphe (DR) and ventral tegmental area (VTA) activates the fibers of the same reward pathway but the phenotype of this pathway and the direction of the reward-relevant fibers have not been determined. Here we report rewarding effects following activation of a DR-originating pathway consisting of vesicular glutamate transporter 3 (VGluT3) containing neurons that form asymmetric synapses onto VTA dopamine neurons that project to nucleus accumbens. Optogenetic VTA activation of this projection elicits AMPA-mediated synaptic excitatory currents in VTA mesoaccumbens dopaminergic neurons and causes dopamine release innucleus accumbens. Activation also reinforces instrumental behavior and establishes conditioned place preferences. These findings indicate that the DR-VGluT3 pathway to VTA utilizes glutamate as a neurotransmitter and is a substrate linking the DR—one of the most sensitive reward sites in the brain—to VTA dopaminergic neurons. PMID:25388237

  2. Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

    PubMed Central

    Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge

    2014-01-01

    Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543

  3. ENERGY REGULATORY SIGNALS AND FOOD REWARD

    PubMed Central

    Figlewicz, Dianne P.; Sipols, Alfred J.

    2010-01-01

    The hormones insulin, leptin, and ghrelin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis, acting at medial hypothalamic sites. Here, we summarize research demonstrating that, in addition to direct homeostatic actions at the hypothalamus, CNS circuitry that subserves reward and is also a direct and indirect target for the action of these endocrine regulators of energy homeostasis. Specifically, insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward, the midbrain dopamine (DA) and opioidergic pathways. Ghrelin can increase food reward behaviors, and support midbrain DA neuronal function. We summarize discussion of behavioral, systems, and cellular evidence in support of the contributions of reward circuitry to the homeostatic roles of these hormones in the CNS. The understanding of neuroendocrine modulation of food reward, as well as food reward modulation by diet and obesity, may point to new directions for therapeutic approaches to overeating or eating disorders. PMID:20230849

  4. Rewards and advancements for clinical pharmacists.

    PubMed

    Goodwin, S Diane; Kane-Gill, Sandra L; Ng, Tien M H; Melroy, Joel T; Hess, Mary M; Tallian, Kimberly; Trujillo, Toby C; Vermeulen, Lee C

    2010-01-01

    The American College of Clinical Pharmacy charged the Clinical Practice Affairs Committee to review and update the College's 1995 White Paper, "Rewards and Advancements for Clinical Pharmacy Practitioners." Because of the limited data on the present state of rewards and advancements for clinical pharmacists, an online survey of "front-line" clinical pharmacists and pharmacy managers was conducted (1126 total respondents, 14% response rate). The resulting White Paper discusses motivators and existing systems of rewards and advancements for clinical pharmacists, as well as perceived barriers to implementation of these systems. Clinical pharmacists reported work-life balance, a challenging position, and opportunities for professional advancement as the most important factors for career success. At the time of the survey, financial rewards appeared not to be a major motivator for clinical pharmacists. Managers underestimated the importance that clinical pharmacists place on work-life balance and favorable work schedules. Although almost two thirds of the clinical pharmacists surveyed had not developed a professional development plan, 84% indicated an interest in career planning. Both clinical pharmacists and managers rated the lack of a clear reward and advancement structure as the most important barrier to effective systems of rewards and advancements. Pharmacy managers and administrators are encouraged to develop effective systems of rewards and advancements for clinical pharmacists that positively impact patient care and the institution's mission; these systems will benefit the clinical pharmacist, the health care institution, and the patient. PMID:20030483

  5. Reward Systems in the Brain and Nutrition.

    PubMed

    Rolls, Edmund T

    2016-07-17

    The taste cortex in the anterior insula provides separate and combined representations of the taste, temperature, and texture of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are combined by associative learning with olfactory and visual inputs for some neurons, and these neurons encode food reward value in that they respond to food only when hunger is present and in that activations correlate linearly with subjective pleasantness. Cognitive factors, including word-level descriptions and selective attention to affective value, modulate the representation of the reward value of taste, olfactory, and flavor stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex. These food reward representations are important in the control of appetite and food intake. Individual differences in reward representations may contribute to obesity, and there are age-related differences in these reward representations. Implications of how reward systems in the brain operate for understanding, preventing, and treating obesity are described. PMID:27146018

  6. Empathy Modulates the Rewarding Effect of Mimicry

    PubMed Central

    Neufeld, J.; Chakrabarti, B.

    2016-01-01

    We tend to like those who mimic us. In this study we formally test if mimicry changes the reward value of the mimicker, using gaze bias as a proxy for reward. Previous research has demonstrated that people show gaze bias towards more rewarding targets, suggesting that gaze bias can be considered a proxy for relative reward value. Forty adults participated in a conditioning task, where they were mimicked by one face and ‘anti-mimicked’ by another. Subsequently, they were found to show gaze-bias towards faces that mimicked them compared to those that did not, in a preferential looking task. The strength of this effect correlated positively with individual levels of trait empathy. In a separate, similar task, these participants showed a gaze bias for faces paired with high vs low monetary rewards, thus validating the use of gaze bias as a proxy for learnt reward. Together, these results demonstrate that mimicry changes the reward value of social stimuli, and empathy influences the extent of this change. This can potentially inform conditions marked by deficits in forming social bonds, such as Autism. PMID:27297317

  7. Empathy Modulates the Rewarding Effect of Mimicry.

    PubMed

    Neufeld, J; Chakrabarti, B

    2016-01-01

    We tend to like those who mimic us. In this study we formally test if mimicry changes the reward value of the mimicker, using gaze bias as a proxy for reward. Previous research has demonstrated that people show gaze bias towards more rewarding targets, suggesting that gaze bias can be considered a proxy for relative reward value. Forty adults participated in a conditioning task, where they were mimicked by one face and 'anti-mimicked' by another. Subsequently, they were found to show gaze-bias towards faces that mimicked them compared to those that did not, in a preferential looking task. The strength of this effect correlated positively with individual levels of trait empathy. In a separate, similar task, these participants showed a gaze bias for faces paired with high vs low monetary rewards, thus validating the use of gaze bias as a proxy for learnt reward. Together, these results demonstrate that mimicry changes the reward value of social stimuli, and empathy influences the extent of this change. This can potentially inform conditions marked by deficits in forming social bonds, such as Autism. PMID:27297317

  8. MOSAIC for multiple-reward environments.

    PubMed

    Sugimoto, Norikazu; Haruno, Masahiko; Doya, Kenji; Kawato, Mitsuo

    2012-03-01

    Reinforcement learning (RL) can provide a basic framework for autonomous robots to learn to control and maximize future cumulative rewards in complex environments. To achieve high performance, RL controllers must consider the complex external dynamics for movements and task (reward function) and optimize control commands. For example, a robot playing tennis and squash needs to cope with the different dynamics of a tennis or squash racket and such dynamic environmental factors as the wind. In addition, this robot has to tailor its tactics simultaneously under the rules of either game. This double complexity of the external dynamics and reward function sometimes becomes more complex when both the multiple dynamics and multiple reward functions switch implicitly, as in the situation of a real (multi-agent) game of tennis where one player cannot observe the intention of her opponents or her partner. The robot must consider its opponent's and its partner's unobservable behavioral goals (reward function). In this article, we address how an RL agent should be designed to handle such double complexity of dynamics and reward. We have previously proposed modular selection and identification for control (MOSAIC) to cope with nonstationary dynamics where appropriate controllers are selected and learned among many candidates based on the error of its paired dynamics predictor: the forward model. Here we extend this framework for RL and propose MOSAIC-MR architecture. It resembles MOSAIC in spirit and selects and learns an appropriate RL controller based on the RL controller's TD error using the errors of the dynamics (the forward model) and the reward predictors. Furthermore, unlike other MOSAIC variants for RL, RL controllers are not a priori paired with the fixed predictors of dynamics and rewards. The simulation results demonstrate that MOSAIC-MR outperforms other counterparts because of this flexible association ability among RL controllers, forward models, and reward

  9. Extending overjustification: the effect of perceived reward-giver intention on response to rewards.

    PubMed

    Forehand, M R

    2000-12-01

    The perceived intention model incorporates a new moderator, beliefs about reward-giver intention, into the overjustification paradigm. In 2 simulated shopping studies featuring products paired with promotional rewards, consumers who believed the marketer was promotion focused (reward used to encourage purchase) reported lower purchase intentions and brand attitudes for promoted products after promotion, whereas consumers who believed the marketer was reward focused (promotion used to distribute the reward) showed no attitude change. Promotion-focus beliefs lowered attitudes by heightening the contingency between the promotion and purchase and thereby increasing the perceived causal role of the reward. This effect was contingent on initial behavior--postpromotion attitude change occurred for consumers who actively engaged in product decisions but not for consumers who passively observed the choice sets. PMID:11125656

  10. Prior fear conditioning and reward learning interact in fear and reward networks

    PubMed Central

    Bulganin, Lisa; Bach, Dominik R.; Wittmann, Bianca C.

    2014-01-01

    The ability to flexibly adapt responses to changes in the environment is important for survival. Previous research in humans separately examined the mechanisms underlying acquisition and extinction of aversive and appetitive conditioned responses. It is yet unclear how aversive and appetitive learning interact on a neural level during counterconditioning in humans. This functional magnetic resonance imaging (fMRI) study investigated the interaction of fear conditioning and subsequent reward learning. In the first phase (fear acquisition), images predicted aversive electric shocks or no aversive outcome. In the second phase (counterconditioning), half of the CS+ and CS− were associated with monetary reward in the absence of electric stimulation. The third phase initiated reinstatement of fear through presentation of electric shocks, followed by CS presentation in the absence of shock or reward. Results indicate that participants were impaired at learning the reward contingencies for stimuli previously associated with shock. In the counterconditioning phase, prior fear association interacted with reward representation in the amygdala, where activation was decreased for rewarded compared to unrewarded CS− trials, while there was no reward-related difference in CS+ trials. In the reinstatement phase, an interaction of previous fear association and previous reward status was observed in a reward network consisting of substantia nigra/ventral tegmental area (SN/VTA), striatum and orbitofrontal cortex (OFC), where activation was increased by previous reward association only for CS− but not for CS+ trials. These findings suggest that during counterconditioning, prior fear conditioning interferes with reward learning, subsequently leading to lower activation of the reward network. PMID:24624068

  11. The differential influences of positive affect, random reward, and performance-contingent reward on cognitive control.

    PubMed

    Fröber, Kerstin; Dreisbach, Gesine

    2014-06-01

    Growing evidence suggests that positive affect and reward have differential effects on cognitive control. So far, however, these effects have never been studied together. Here, the authors present one behavioral study investigating the influences of positive affect and reward (contingent and noncontingent) on proactive control. A modified version of the AX-continuous performance task, which has repeatedly been shown to be sensitive to reward and affect manipulations, was used. In a first phase, two experimental groups received either neutral or positive affective pictures before every trial. In a second phase, the two halves of a given affect group additionally received, respectively, performance-contingent or random rewards. The results replicated the typical affect effect, in terms of reduced proactive control under positive as compared to neutral affect. Also, the typical reward effects associated with increased proactive control were replicated. Most interestingly, performance-contingent reward counteracted the positive affect effect, whereas random reward mirrored that effect. In sum, this study provides first evidence that performance-contingent reward, on the one hand, and positive affect and performance-noncontingent reward, on the other hand, have oppositional effects on cognitive control: Only performance-contingent reward showed a motivational effect in terms of a strategy shift toward increased proactive control, whereas positive affect alone and performance-noncontingent reward reduced proactive control. Moreover, the integrative design of this study revealed the vulnerability of positive affect effects to motivational manipulations. The results are discussed with respect to current neuroscientific theories of the effects of dopamine on affect, reward, and cognitive control. PMID:24659000

  12. Effects of anabolic-androgens on brain reward function.

    PubMed

    Mhillaj, Emanuela; Morgese, Maria G; Tucci, Paolo; Bove, Maria; Schiavone, Stefania; Trabace, Luigia

    2015-01-01

    Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies. PMID:26379484

  13. Effects of anabolic-androgens on brain reward function

    PubMed Central

    Mhillaj, Emanuela; Morgese, Maria G.; Tucci, Paolo; Bove, Maria; Schiavone, Stefania; Trabace, Luigia

    2015-01-01

    Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies. PMID:26379484

  14. The Brain Reward Circuitry in Mood Disorders

    PubMed Central

    Russo, Scott J.; Nestler, Eric J.

    2013-01-01

    Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioral domains. A recent literature has identified important structural and functional alterations within the brain’s reward circuitry —particularly in the ventral tegmental area to nucleus accumbens pathway — that are associated with symptoms such as anhedonia and aberrant reward-associated perception and memory. This review synthesizes recent data from human and rodent studies from which emerges a circuit-level framework for understanding reward deficits in depression. We also discuss some of the molecular and cellular underpinnings of this framework, ranging from adaptations in glutamatergic synapses and neurotrophic factors to transcriptional and epigenetic mechanisms. PMID:23942470

  15. Discounting of sequences of delayed rewards of different amounts.

    PubMed

    Białaszek, Wojciech; Ostaszewski, Paweł

    2012-01-01

    The main purpose of this study was to determine whether the magnitude effect is present in cases where delayed sequences of rewards are discounted. The magnitude effect refers to the inverse relationship between the amount of a reward and the steepness of temporal discounting. This study was conducted with a computer program to estimate the indifference points, which served as indicators of the present subjective value of delayed sequences of small and large rewards. In the indifference point the subjective value of a single, immediate reward was equal to the subjective value of the delayed sequence (or to the value of a single delayed reward). As a control condition, we added an experimental task involving choices between single immediate and single delayed rewards. The experiment showed that the sequences of large rewards are discounted less steeply than are the sequences of small rewards. This finding suggests that the magnitude effect is present within the delayed sequences of rewards. In addition, when outcomes are relatively large, the results suggest that a single reward is discounted less steeply than the sequence of a total nominal value equal to this single reward. However, for relatively small rewards, the difference is not statistically significant. The less steep discounting of sequences of large rewards may explain the reward-bundling effect, which refers to less steep discounting of longer sequences than of shorter ones: longer sequences usually have greater overall nominal value. The present study was conducted on hypothetical rewards, and the results should be validated using real rewards. PMID:22062547

  16. Dorsomedial striatum lesions affect adjustment to reward uncertainty, but not to reward devaluation or omission.

    PubMed

    Torres, Carmen; Glueck, Amanda C; Conrad, Shannon E; Morón, Ignacio; Papini, Mauricio R

    2016-09-22

    The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons. PMID:27365171

  17. Motivating interdependent teams: individual rewards, shared rewards, or something in between?

    PubMed

    Pearsall, Matthew J; Christian, Michael S; Ellis, Aleksander P J

    2010-01-01

    The primary purpose in this study was to extend theory and research regarding the motivational process in teams by examining the effects of hybrid rewards on team performance. Further, to better understand the underlying team level mechanisms, the authors examined whether the hypothesized benefits of hybrid over shared and individual rewards were due to increased information allocation and reduced social loafing. Results from 90 teams working on a command-and-control simulation supported the hypotheses. Hybrid rewards led to higher levels of team performance than did individual and shared rewards; these effects were due to improvements in information allocation and reductions in social loafing. PMID:20085415

  18. Segregated encoding of reward-identity and stimulus-reward associations in human orbitofrontal cortex.

    PubMed

    Klein-Flügge, Miriam Cornelia; Barron, Helen Catharine; Brodersen, Kay Henning; Dolan, Raymond J; Behrens, Timothy Edward John

    2013-02-13

    A dominant focus in studies of learning and decision-making is the neural coding of scalar reward value. This emphasis ignores the fact that choices are strongly shaped by a rich representation of potential rewards. Here, using fMRI adaptation, we demonstrate that responses in the human orbitofrontal cortex (OFC) encode a representation of the specific type of food reward predicted by a visual cue. By controlling for value across rewards and by linking each reward with two distinct stimuli, we could test for representations of reward-identity that were independent of associative information. Our results show reward-identity representations in a medial-caudal region of OFC, independent of the associated predictive stimulus. This contrasts with a more rostro-lateral OFC region encoding reward-identity representations tied to the predicate stimulus. This demonstration of adaptation in OFC to reward specific representations opens an avenue for investigation of more complex decision mechanisms that are not immediately accessible in standard analyses, which focus on correlates of average activity. PMID:23407973

  19. The Circadian Clock, Reward, and Memory

    PubMed Central

    Albrecht, Urs

    2011-01-01

    During our daily activities, we experience variations in our cognitive performance, which is often accompanied by cravings for small rewards, such as consuming coffee or chocolate. This indicates that the time of day, cognitive performance, and reward may be related to one another. This review will summarize data that describe the influence of the circadian clock on addiction and mood-related behavior and put the data into perspective in relation to memory processes. PMID:22084628

  20. Brain structural substrates of reward dependence during behavioral performance.

    PubMed

    Dayan, Eran; Hamann, Janne M; Averbeck, Bruno B; Cohen, Leonardo G

    2014-12-01

    Interindividual differences in the effects of reward on performance are prevalent and poorly understood, with some individuals being more dependent than others on the rewarding outcomes of their actions. The origin of this variability in reward dependence is unknown. Here, we tested the relationship between reward dependence and brain structure in healthy humans. Subjects trained on a visuomotor skill-acquisition task and received performance feedback in the presence or absence of reward. Reward dependence was defined as the statistical trial-by-trial relation between reward and subsequent performance. We report a significant relationship between reward dependence and the lateral prefrontal cortex, where regional gray-matter volume predicted reward dependence but not feedback alone. Multivoxel pattern analysis confirmed the anatomical specificity of this relationship. These results identified a likely anatomical marker for the prospective influence of reward on performance, which may be of relevance in neurorehabilitative settings. PMID:25471581

  1. Characterising reward outcome signals in sensory cortex☆

    PubMed Central

    FitzGerald, Thomas H.B.; Friston, Karl J.; Dolan, Raymond J.

    2013-01-01

    Reward outcome signalling in the sensory cortex is held as important for linking stimuli to their consequences and for modulating perceptual learning in response to incentives. Evidence for reward outcome signalling has been found in sensory regions including the visual, auditory and somatosensory cortices across a range of different paradigms, but it is unknown whether the population of neurons signalling rewarding outcomes are the same as those processing predictive stimuli. We addressed this question using a multivariate analysis of high-resolution functional magnetic resonance imaging (fMRI), in a task where subjects were engaged in instrumental learning with visual predictive cues and auditory signalled reward feedback. We found evidence that outcome signals in sensory regions localise to the same areas involved in stimulus processing. These outcome signals are non-specific and we show that the neuronal populations involved in stimulus representation are not their exclusive target, in keeping with theoretical models of value learning. Thus, our results reveal one likely mechanism through which rewarding outcomes are linked to predictive sensory stimuli, a link that may be key for both reward and perceptual learning. PMID:23811411

  2. Anabolic-androgenic steroids and brain reward.

    PubMed

    Clark, A S; Lindenfeld, R C; Gibbons, C H

    1996-03-01

    Anabolic-androgenic steroid (AAS) effects on brain reward were investigated in male rats with electrodes implanted in the lateral hypothalamus using the rate-frequency curve shift paradigm of brain stimulation reward. In the first experiment, treatment for 2 weeks with the AAS methandrostenolone had no effect on either the reward or performance components of intracranial self-stimulation. In the second experiment, treatment for 15 weeks with an AAS "cocktail" consisting of testosterone cypionate, nandrolone decanoate, and boldenone undecylenate did not alter brain reward but did produce a slight but significant change in bar press rate. In addition to the AAS treatment, animals in the second study were administered a single injection of d-amphetamine before and after 15 weeks of AAS exposure. The rate-frequency curve shift observed in response to a systemic injection of amphetamine was significantly greater in animals after 15 weeks of treatment with the AAS cocktail. Although AAS do not appear to alter the rewarding properties of brain stimulation, AAS may influence the sensitivity of brain reward systems. PMID:8866980

  3. Musical pleasure and reward: mechanisms and dysfunction.

    PubMed

    Zatorre, Robert J

    2015-03-01

    Most people derive pleasure from music. Neuroimaging studies show that the reward system of the human brain is central to this experience. Specifically, the dorsal and ventral striatum release dopamine when listening to pleasurable music, and activity in these structures also codes the reward value of musical excerpts. Moreover, the striatum interacts with cortical mechanisms involved in perception and valuation of musical stimuli. Recent studies have begun to explore individual differences in the way that this complex system functions. Development of a questionnaire for music reward experiences has allowed the identification of separable factors associated with musical pleasure, described as music-seeking, emotion-evocation, mood regulation, sensorimotor, and social factors. Applying this questionnaire to a large sample uncovered approximately 5% of the population with low sensitivity to musical reward in the absence of generalized anhedonia or depression. Further study of this group revealed that there are individuals who respond normally both behaviorally and psychophysiologically to rewards other than music (e.g., monetary value) but do not experience pleasure from music despite normal music perception ability and preserved ability to identify intended emotions in musical passages. This specific music anhedonia bears further study, as it may shed light on the function and dysfunction of the reward system. PMID:25773636

  4. Adolescent behavioral and neural reward sensitivity: a test of the differential susceptibility theory.

    PubMed

    Richards, J S; Arias Vásquez, A; von Rhein, D; van der Meer, D; Franke, B; Hoekstra, P J; Heslenfeld, D J; Oosterlaan, J; Faraone, S V; Buitelaar, J K; Hartman, C A

    2016-01-01

    Little is known about the causes of individual differences in reward sensitivity. We investigated gene-environment interactions (GxE) on behavioral and neural measures of reward sensitivity, in light of the differential susceptibility theory. This theory states that individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Reward responses were assessed during a monetary incentive delay task in 178 participants with and 265 without attention-deficit/hyperactivity disorder (ADHD), from N=261 families. We examined interactions between variants in candidate plasticity genes (DAT1, 5-HTT and DRD4) and social environments (maternal expressed emotion and peer affiliation). HTTLPR short allele carriers showed the least reward speeding when exposed to high positive peer affiliation, but the most when faced with low positive peer affiliation or low maternal warmth. DAT1 10-repeat homozygotes displayed similar GxE patterns toward maternal warmth on general task performance. At the neural level, DRD4 7-repeat carriers showed the least striatal activation during reward anticipation when exposed to high maternal warmth, but the most when exposed to low warmth. Findings were independent of ADHD severity. Our results partially confirm the differential susceptibility theory and indicate the importance of positive social environments in reward sensitivity and general task performance for persons with specific genotypes. PMID:27045841

  5. Adolescent behavioral and neural reward sensitivity: a test of the differential susceptibility theory

    PubMed Central

    Richards, J S; Arias Vásquez, A; von Rhein, D; van der Meer, D; Franke, B; Hoekstra, P J; Heslenfeld, D J; Oosterlaan, J; Faraone, S V; Buitelaar, J K; Hartman, C A

    2016-01-01

    Little is known about the causes of individual differences in reward sensitivity. We investigated gene–environment interactions (GxE) on behavioral and neural measures of reward sensitivity, in light of the differential susceptibility theory. This theory states that individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Reward responses were assessed during a monetary incentive delay task in 178 participants with and 265 without attention-deficit/hyperactivity disorder (ADHD), from N=261 families. We examined interactions between variants in candidate plasticity genes (DAT1, 5-HTT and DRD4) and social environments (maternal expressed emotion and peer affiliation). HTTLPR short allele carriers showed the least reward speeding when exposed to high positive peer affiliation, but the most when faced with low positive peer affiliation or low maternal warmth. DAT1 10-repeat homozygotes displayed similar GxE patterns toward maternal warmth on general task performance. At the neural level, DRD4 7-repeat carriers showed the least striatal activation during reward anticipation when exposed to high maternal warmth, but the most when exposed to low warmth. Findings were independent of ADHD severity. Our results partially confirm the differential susceptibility theory and indicate the importance of positive social environments in reward sensitivity and general task performance for persons with specific genotypes. PMID:27045841

  6. Role of dopamine tone in the pursuit of brain stimulation reward.

    PubMed

    Hernandez, Giovanni; Trujillo-Pisanty, Ivan; Cossette, Marie-Pierre; Conover, Kent; Shizgal, Peter

    2012-08-01

    Dopaminergic neurons contribute to intracranial self-stimulation (ICSS) and other reward-seeking behaviors, but it is not yet known where dopaminergic neurons intervene in the neural circuitry underlying reward pursuit or which psychological processes are involved. In rats working for electrical stimulation of the medial forebrain bundle, we assessed the effect of GBR-12909 (1-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-4-[3- phenylpropyl]piperazine), a specific blocker of the dopamine transporter. Operant performance was measured as a function of the strength and cost of electrical stimulation. GBR-12909 increased the opportunity cost most subjects were willing to pay for a reward of a given intensity. However, this effect was smaller than that produced by a regimen of cocaine administration that drove similar increases in nucleus accumbens (NAc) dopamine levels in unstimulated rats. Delivery of rewarding stimulation to drug-treated rats caused an additional increase in dopamine concentration in the NAc shell in cocaine-treated, but not GBR-12909-treated, rats. These behavioral and neurochemical differences may reflect blockade of the norepinephrine transporter by cocaine but not by GBR-12909. Whereas the effect of psychomotor stimulants on ICSS has long been attributed to dopaminergic action at early stages of the reward pathway, the results reported here imply that increased dopamine tone boosts reward pursuit by acting at or beyond the output of the circuitry that temporally and spatially summates the output of the directly stimulated neurons underlying ICSS. The observed enhancement of reward seeking could be attributable to a decrease in the value of competing behaviors, a decrease in subjective effort costs, or an increase in reward-system gain. PMID:22875936

  7. "Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

    PubMed

    Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

    2012-01-01

    In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily selfadministered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions. PMID:22236117

  8. Reward sensitivity for a palatable food reward peaks during pubertal developmental in rats.

    PubMed

    Friemel, Chris M; Spanagel, Rainer; Schneider, Miriam

    2010-01-01

    Puberty is a critical period for the initiation of drug use and abuse. Because early drug use onset often accounts for a more severe progression of addiction, it is of importance to understand the underlying mechanisms and neurodevelopmental changes during puberty that are contributing to enhanced reward processing in teenagers. The present study investigated the progression of reward sensitivity toward a natural food reward over the whole course of adolescence in male rats (postnatal days 30-90) by monitoring consummatory, motivational behavior and neurobiological correlates of reward. Using a limited-free intake paradigm, consumption of sweetened condensed milk (SCM) was measured repeatedly in adolescent and adult rats. Additionally, early- and mid-pubertal animals were tested in Progressive Ratio responding for SCM and c-fos protein expression in reward-associated brain structures was examined after odor conditioning for SCM. We found a transient increase in SCM consumption and motivational incentive for SCM during puberty. This increased reward sensitivity was most pronounced around mid-puberty. The behavioral findings are paralleled by enhanced c-fos staining in reward-related structures revealing an intensified neuronal response after reward-cue presentation, distinctive for pubertal animals. Taken together, these data indicate an increase in reward sensitivity during adolescence accompanied by enhanced responsiveness of reward-associated brain structures to incentive stimuli, and it seems that both is strongly pronounced around mid-puberty. Therefore, higher reward sensitivity during pubertal maturation might contribute to the enhanced vulnerability of teenagers for the initiation of experimental drug use. PMID:20700386

  9. Modulation of neural activity by reward in medial intraparietal cortex is sensitive to temporal sequence of reward

    PubMed Central

    Rajalingham, Rishi; Stacey, Richard Greg; Tsoulfas, Georgios

    2014-01-01

    To restore movements to paralyzed patients, neural prosthetic systems must accurately decode patients' intentions from neural signals. Despite significant advancements, current systems are unable to restore complex movements. Decoding reward-related signals from the medial intraparietal area (MIP) could enhance prosthetic performance. However, the dynamics of reward sensitivity in MIP is not known. Furthermore, reward-related modulation in premotor areas has been attributed to behavioral confounds. Here we investigated the stability of reward encoding in MIP by assessing the effect of reward history on reward sensitivity. We recorded from neurons in MIP while monkeys performed a delayed-reach task under two reward schedules. In the variable schedule, an equal number of small- and large-rewards trials were randomly interleaved. In the constant schedule, one reward size was delivered for a block of trials. The memory period firing rate of most neurons in response to identical rewards varied according to schedule. Using systems identification tools, we attributed the schedule sensitivity to the dependence of neural activity on the history of reward. We did not find schedule-dependent behavioral changes, suggesting that reward modulates neural activity in MIP. Neural discrimination between rewards was less in the variable than in the constant schedule, degrading our ability to decode reach target and reward simultaneously. The effect of schedule was mitigated by adding Haar wavelet coefficients to the decoding model. This raises the possibility of multiple encoding schemes at different timescales and reinforces the potential utility of reward information for prosthetic performance. PMID:25008408

  10. Reproductive isolation and pollination success of rewarding Galearis diantha and non-rewarding Ponerorchis chusua (Orchidaceae)

    PubMed Central

    Sun, Hai-Qin; Huang, Bao-Qiang; Yu, Xiao-Hong; Kou, Yong; An, De-Jun; Luo, Yi-Bo; Ge, Song

    2011-01-01

    Background and Aims Increasing evidence challenges the conventional perception that orchids are the most distinct example of floral diversification due to floral or prezygotic isolation. Regarding the relationship between co-flowering plants, rewarding and non-rewarding orchids in particular, few studies have investigated whether non-rewarding plants affect the pollination success of rewarding plants. Here, floral isolation and mutual effects between the rewarding orchid Galearis diantha and the non-rewarding orchid Ponerorchis chusua were investigated. Methods Flowering phenological traits were monitored by noting the opening and wilting dates of the chosen individual plants. The pollinator pool and pollinator behaviour were assessed from field observations. Key morphological traits of the flowers and pollinators were measured directly in the field. Pollinator limitation and interspecific compatibility were evaluated by hand-pollination experiments. Fruit set was surveyed in monospecific and heterospecific plots. Key Results The species had overlapping peak flowering periods. Pollinators of both species displayed a certain degree of constancy in visiting each species, but they also visited other flowers before landing on the focal orchids. A substantial difference in spur size between the species resulted in the deposition of pollen on different regions of the body of the shared pollinator. Hand-pollination experiments revealed that fruit set was strongly pollinator-limited in both species. No significant difference in fruit set was found between monospecific plots and heterospecific plots. Conclusions A combination of mechanical isolation and incomplete ethological isolation eliminates the possibility of pollen transfer between the species. These results do not support either the facilitation or competition hypothesis regarding the effect of nearby rewarding flowers on non-rewarding plants. The absence of a significant effect of non-rewarding P. chusua on

  11. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?

    PubMed

    Berridge, K C; Robinson, T E

    1998-12-01

    What roles do mesolimbic and neostriatal dopamine systems play in reward? Do they mediate the hedonic impact of rewarding stimuli? Do they mediate hedonic reward learning and associative prediction? Our review of the literature, together with results of a new study of residual reward capacity after dopamine depletion, indicates the answer to both questions is 'no'. Rather, dopamine systems may mediate the incentive salience of rewards, modulating their motivational value in a manner separable from hedonia and reward learning. In a study of the consequences of dopamine loss, rats were depleted of dopamine in the nucleus accumbens and neostriatum by up to 99% using 6-hydroxydopamine. In a series of experiments, we applied the 'taste reactivity' measure of affective reactions (gapes, etc.) to assess the capacity of dopamine-depleted rats for: 1) normal affect (hedonic and aversive reactions), 2) modulation of hedonic affect by associative learning (taste aversion conditioning), and 3) hedonic enhancement of affect by non-dopaminergic pharmacological manipulation of palatability (benzodiazepine administration). We found normal hedonic reaction patterns to sucrose vs. quinine, normal learning of new hedonic stimulus values (a change in palatability based on predictive relations), and normal pharmacological hedonic enhancement of palatability. We discuss these results in the context of hypotheses and data concerning the role of dopamine in reward. We review neurochemical, electrophysiological, and other behavioral evidence. We conclude that dopamine systems are not needed either to mediate the hedonic pleasure of reinforcers or to mediate predictive associations involved in hedonic reward learning. We conclude instead that dopamine may be more important to incentive salience attributions to the neural representations of reward-related stimuli. Incentive salience, we suggest, is a distinct component of motivation and reward. In other words, dopamine systems are necessary

  12. Three real-time architectures - A study using reward models

    NASA Technical Reports Server (NTRS)

    Sjogren, J. A.; Smith, R. M.

    1990-01-01

    Numerous applications in the area of computer system analysis can be effectively studied with Markov reward models. These models describe the evolutionary behavior of the computer system by a continuous-time Markov chain, and a reward rate is associated with each state. In reliability/availability models, upstates have reward rate 1, and down states have reward rate zero associated with them. In a combined model of performance and reliability, the reward rate of a state may be the computational capacity, or a related performance measure. Steady-state expected reward rate and expected instantaneous reward rate are clearly useful measures which can be extracted from the Markov reward model. The diversity of areas where Markov reward models may be used is illustrated with a comparative study of three examples of interest to the fault tolerant computing community.

  13. Serotonin neurons in the dorsal raphe nucleus encode reward signals

    PubMed Central

    Li, Yi; Zhong, Weixin; Wang, Daqing; Feng, Qiru; Liu, Zhixiang; Zhou, Jingfeng; Jia, Chunying; Hu, Fei; Zeng, Jiawei; Guo, Qingchun; Fu, Ling; Luo, Minmin

    2016-01-01

    The dorsal raphe nucleus (DRN) is involved in organizing reward-related behaviours; however, it remains unclear how genetically defined neurons in the DRN of a freely behaving animal respond to various natural rewards. Here we addressed this question using fibre photometry and single-unit recording from serotonin (5-HT) neurons and GABA neurons in the DRN of behaving mice. Rewards including sucrose, food, sex and social interaction rapidly activate 5-HT neurons, but aversive stimuli including quinine and footshock do not. Both expected and unexpected rewards activate 5-HT neurons. After mice learn to wait for sucrose delivery, most 5-HT neurons fire tonically during waiting and then phasically on reward acquisition. Finally, GABA neurons are activated by aversive stimuli but inhibited when mice seek rewards. Thus, DRN 5-HT neurons positively encode a wide range of reward signals during anticipatory and consummatory phases of reward responses. Moreover, GABA neurons play a complementary role in reward processing. PMID:26818705

  14. Serotonin neurons in the dorsal raphe nucleus encode reward signals.

    PubMed

    Li, Yi; Zhong, Weixin; Wang, Daqing; Feng, Qiru; Liu, Zhixiang; Zhou, Jingfeng; Jia, Chunying; Hu, Fei; Zeng, Jiawei; Guo, Qingchun; Fu, Ling; Luo, Minmin

    2016-01-01

    The dorsal raphe nucleus (DRN) is involved in organizing reward-related behaviours; however, it remains unclear how genetically defined neurons in the DRN of a freely behaving animal respond to various natural rewards. Here we addressed this question using fibre photometry and single-unit recording from serotonin (5-HT) neurons and GABA neurons in the DRN of behaving mice. Rewards including sucrose, food, sex and social interaction rapidly activate 5-HT neurons, but aversive stimuli including quinine and footshock do not. Both expected and unexpected rewards activate 5-HT neurons. After mice learn to wait for sucrose delivery, most 5-HT neurons fire tonically during waiting and then phasically on reward acquisition. Finally, GABA neurons are activated by aversive stimuli but inhibited when mice seek rewards. Thus, DRN 5-HT neurons positively encode a wide range of reward signals during anticipatory and consummatory phases of reward responses. Moreover, GABA neurons play a complementary role in reward processing. PMID:26818705

  15. Rewarded visual items capture attention only in heterogeneous contexts.

    PubMed

    Feldmann-Wüstefeld, Tobias; Brandhofer, Ruben; Schubö, Anna

    2016-07-01

    Reward is known to affect visual search performance. Rewarding targets can increase search performance, whereas rewarding distractors can decrease search performance. We used subcomponents of the N2pc in the event-related EEG, the NT (target negativity) and ND /PD (distractor negativity/positivity), in a visual search task to disentangle target and distractor processing related to reward. The visual search task comprised homogeneous and heterogeneous contexts in which a target and a colored distractor were embedded. After each correct trial, participants were given a monetary reward that depended on the color of the distractor. We found longer response times for displays with high-reward distractors compared to displays with low-reward distractors, indicating reward-induced interference, however, only for heterogeneous contexts. The NT component, indicative of attention deployment to the target, showed that target selection was impaired by high-reward distractors, regardless of the context homogeneity. Processing of distractors was not affected by reward in homogeneous contexts. In heterogeneous contexts, however, high-reward distractors were more likely to capture attention (ND ) and required more effort to be suppressed (PD ) than low-reward distractors. In sum the results showed that, despite the fact that target selection is impaired by high-reward distractors in both homogeneous and heterogeneous background contexts, high-reward distractors capture attention only in scenarios that foster attentional capture. PMID:26997364

  16. Listening to music in a risk-reward context: The roles of the temporoparietal junction and the orbitofrontal/insular cortices in reward-anticipation, reward-gain, and reward-loss.

    PubMed

    Li, Chia-Wei; Chen, Jyh-Horng; Tsai, Chen-Gia

    2015-12-10

    Artificial rewards, such as visual arts and music, produce pleasurable feelings. Popular songs in the verse-chorus form provide a useful model for understanding the neural mechanisms underlying the processing of artificial rewards, because the chorus is usually the most rewarding element of a song. In this functional magnetic resonance imaging (fMRI) study, the stimuli were excerpts of 10 popular songs with a tensioned verse-to-chorus transition. We examined the neural correlates of three phases of reward processing: (1) reward-anticipation during the verse-to-chorus transition, (2) reward-gain during the first phrase of the chorus, and (3) reward-loss during the unexpected noise followed by the verse-to-chorus transition. Participants listened to these excerpts in a risk-reward context because the verse was followed by either the chorus or noise with equal probability. The results showed that reward-gain and reward-loss were associated with left- and right-biased temporoparietal junction activation, respectively. The bilateral temporoparietal junctions were active during reward-anticipation. Moreover, we observed left-biased lateral orbitofrontal activation during reward-anticipation, whereas the medial orbitofrontal cortex was activated during reward-gain. The findings are discussed in relation to the cognitive and emotional aspects of reward processing. PMID:26499261

  17. Distinct Reward Properties are Encoded via Corticostriatal Interactions

    PubMed Central

    Smith, David V.; Rigney, Anastasia E.; Delgado, Mauricio R.

    2016-01-01

    The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nucleus accumbens, a subregion of the striatum. Striatal responses to informative, but not affective, reward properties predicted subsequent utilization of information for obtaining monetary reward. We hypothesized that activation of the striatum may be necessary but not sufficient to encode distinct reward properties. To investigate this possibility, we examined whether affective and informative reward properties were differentially encoded in corticostriatal interactions. Strikingly, we found that the striatum exhibited dissociable connectivity patterns with the ventrolateral prefrontal cortex, with increasing connectivity for affective reward properties and decreasing connectivity for informative reward properties. Our results demonstrate that affective and informative reward properties are encoded via corticostriatal interactions. These findings highlight how corticostriatal systems contribute to reward processing, potentially advancing models linking striatal activation to behavior. PMID:26831208

  18. Reward disrupts reactivated human skill memory

    PubMed Central

    Dayan, Eran; Laor-Maayany, Rony; Censor, Nitzan

    2016-01-01

    Accumulating evidence across species and memory domains shows that when an existing memory is reactivated, it becomes susceptible to modifications. However, the potential role of reward signals in these mechanisms underlying human memory dynamics is unknown. Leaning on a wealth of findings on the role of reward in reinforcing memory, we tested the impact of reinforcing a skill memory trace with monetary reward following memory reactivation, on strengthening of the memory trace. Reinforcing reactivated memories did not strengthen the memory, but rather led to disruption of the memory trace, breaking down the link between memory reactivation and subsequent memory strength. Statistical modeling further revealed a strong mediating role for memory reactivation in linking between memory encoding and subsequent memory strength only when the memory was replayed without reinforcement. We suggest that, rather than reinforcing the existing memory trace, reward creates a competing memory trace, impairing expression of the original reward-free memory. This mechanism sheds light on the processes underlying skill acquisition, having wide translational implications. PMID:27306380

  19. Reward disrupts reactivated human skill memory.

    PubMed

    Dayan, Eran; Laor-Maayany, Rony; Censor, Nitzan

    2016-01-01

    Accumulating evidence across species and memory domains shows that when an existing memory is reactivated, it becomes susceptible to modifications. However, the potential role of reward signals in these mechanisms underlying human memory dynamics is unknown. Leaning on a wealth of findings on the role of reward in reinforcing memory, we tested the impact of reinforcing a skill memory trace with monetary reward following memory reactivation, on strengthening of the memory trace. Reinforcing reactivated memories did not strengthen the memory, but rather led to disruption of the memory trace, breaking down the link between memory reactivation and subsequent memory strength. Statistical modeling further revealed a strong mediating role for memory reactivation in linking between memory encoding and subsequent memory strength only when the memory was replayed without reinforcement. We suggest that, rather than reinforcing the existing memory trace, reward creates a competing memory trace, impairing expression of the original reward-free memory. This mechanism sheds light on the processes underlying skill acquisition, having wide translational implications. PMID:27306380

  20. Dopamine, reward learning, and active inference

    PubMed Central

    FitzGerald, Thomas H. B.; Dolan, Raymond J.; Friston, Karl

    2015-01-01

    Temporal difference learning models propose phasic dopamine signaling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behavior. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings. PMID:26581305

  1. [Influences on the amount of the reward: how five-year-old children distribute rewards].

    PubMed

    Tsutsu, Kiyomi

    2010-08-01

    Five-year-old children were presented two stories in which each of two characters made different numbers of Origami stars; the total number of stars was 16 in one story and 12 in the other. The children allocated rewards to the characters and justified their allocations. There were three conditions in which the total number of rewards was equal to (Middle-N), less than (Small-N), or more than (Large-N) the total number of stars in each story. Most children allocated the rewards equally to the two characters in the Small-N condition, while almost half of the children did not employ an equal allocation in the Middle-N and Large-N conditions. This suggests that in the Small-N condition, if an equity-like allocation were employed, children would feel sorry for the character given very few rewards, and therefore they distributed the rewards equally. On the other hand, in the Middle-N and Large-N conditions, even when one character received fewer rewards than the other, the children did not feel that the fewer rewards were too few. PMID:20845725

  2. Reward from bugs to bipeds: a comparative approach to understanding how reward circuits function

    PubMed Central

    Scaplen, Kristin M.; Kaun, Karla R.

    2016-01-01

    Abstract In a complex environment, animals learn from their responses to stimuli and events. Appropriate response to reward and punishment can promote survival, reproduction and increase evolutionary fitness. Interestingly, the neural processes underlying these responses are remarkably similar across phyla. In all species, dopamine is central to encoding reward and directing motivated behaviors, however, a comprehensive understanding of how circuits encode reward and direct motivated behaviors is still lacking. In part, this is a result of the sheer diversity of neurons, the heterogeneity of their responses and the complexity of neural circuits within which they are found. We argue that general features of reward circuitry are common across model organisms, and thus principles learned from invertebrate model organisms can inform research across species. In particular, we discuss circuit motifs that appear to be functionally equivalent from flies to primates. We argue that a comparative approach to studying and understanding reward circuit function provides a more comprehensive understanding of reward circuitry, and informs disorders that affect the brain’s reward circuitry. PMID:27328845

  3. Reward from bugs to bipeds: a comparative approach to understanding how reward circuits function.

    PubMed

    Scaplen, Kristin M; Kaun, Karla R

    2016-06-01

    In a complex environment, animals learn from their responses to stimuli and events. Appropriate response to reward and punishment can promote survival, reproduction and increase evolutionary fitness. Interestingly, the neural processes underlying these responses are remarkably similar across phyla. In all species, dopamine is central to encoding reward and directing motivated behaviors, however, a comprehensive understanding of how circuits encode reward and direct motivated behaviors is still lacking. In part, this is a result of the sheer diversity of neurons, the heterogeneity of their responses and the complexity of neural circuits within which they are found. We argue that general features of reward circuitry are common across model organisms, and thus principles learned from invertebrate model organisms can inform research across species. In particular, we discuss circuit motifs that appear to be functionally equivalent from flies to primates. We argue that a comparative approach to studying and understanding reward circuit function provides a more comprehensive understanding of reward circuitry, and informs disorders that affect the brain's reward circuitry. PMID:27328845

  4. Employee benefits in a total rewards framework.

    PubMed

    Kwon, Jane; Hein, Pam

    2013-01-01

    Benefits represent one of the largest investments a company makes in its talent. However, our tendency can be to design, deliver and communicate benefits programs independently, without fully considering how those programs fit within a bigger picture of total rewards. Sure, we need to manage and execute individual benefit programs--but not at the expense of getting a real return on our more significant investment in talent. This article provides employers with perspectives on the value of managing benefits within the broader framework of total rewards, why it works and, most importantly, how to make it work. PMID:23488085

  5. MEASURING BELIEFS AND REWARDS: A NEUROECONOMIC APPROACH*

    PubMed Central

    Caplin, Andrew; Dean, Mark; Glimcher, Paul W.; Rutledge, Robb B.

    2014-01-01

    The neurotransmitter dopamine is central to the emerging discipline of neuroeconomics; it is hypothesized to encode the difference between expected and realized rewards and thereby to mediate belief formation and choice. We develop the first formal test of this theory of dopaminergic function, based on a recent axiomatization by Caplin and Dean [2008A]. These tests are satisfied by neural activity in the nucleus accumbens, an area rich in dopamine receptors. We find evidence for separate positive and negative reward prediction error signals, suggesting that behavioral asymmetries in response to losses and gains may parallel asymmetries in nucleus accumbens activity. PMID:25018564

  6. Long term voluntary wheel running is rewarding and produces plasticity in the mesolimbic reward pathway

    PubMed Central

    Greenwood, Benjamin N.; Foley, Teresa E.; Le, Tony V.; Strong, Paul V.; Loughridge, Alice B.; Day, Heidi E.W.; Fleshner, Monika

    2011-01-01

    The mesolimbic reward pathway is implicated in stress-related psychiatric disorders and is a potential target of plasticity underlying the stress resistance produced by repeated voluntary exercise. It is unknown, however, whether rats find long-term access to running wheels rewarding, or if repeated voluntary exercise reward produces plastic changes in mesolimbic reward neurocircuitry. In the current studies, young adult, male Fischer 344 rats allowed voluntary access to running wheels for 6 weeks, but not 2 weeks, found wheel running rewarding, as measured by conditioned place preference (CPP). Consistent with prior reports and the behavioral data, 6 weeks of wheel running increased ΔFosB/FosB immunoreactivity in the nucleus accumbens (Acb). In addition, semi quantitative in situ hybridization revealed that 6 weeks of wheel running, compared to sedentary housing, increased tyrosine hydroxylase (TH) mRNA levels in the ventral tegmental area (VTA), increased delta opioid receptor (DOR) mRNA levels in the Acb shell, and reduced levels of dopamine receptor (DR)-D2 mRNA in the Acb core. Results indicate that repeated voluntary exercise is rewarding and alters gene transcription in mesolimbic reward neurocircuitry. The duration-dependent effects of wheel running on CPP suggest that as the weeks of wheel running progress, the rewarding effects of a night of voluntary wheel running might linger longer into the inactive cycle thus providing stronger support for CPP. The observed plasticity could contribute to the mechanisms by which exercise reduces the incidence and severity of substance abuse disorders, changes the rewarding properties of drugs of abuse, and facilitates successful coping with stress. PMID:21070820

  7. 36 CFR 262.1 - Rewards in connection with fire or property prosecutions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... grass upon the lands of the United States within the National Forest System or nearby. (2) Not exceeding... kindled or caused to be kindled a fire on lands of the United States within the National Forest System or... Agriculture reserves the right to refuse payments of any claim for reward when, in its opinion, collusion...

  8. 36 CFR 262.1 - Rewards in connection with fire or property prosecutions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... grass upon the lands of the United States within the National Forest System or nearby. (2) Not exceeding... kindled or caused to be kindled a fire on lands of the United States within the National Forest System or... Agriculture reserves the right to refuse payments of any claim for reward when, in its opinion, collusion...

  9. 36 CFR 262.1 - Rewards in connection with fire or property prosecutions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... grass upon the lands of the United States within the National Forest System or nearby. (2) Not exceeding... kindled or caused to be kindled a fire on lands of the United States within the National Forest System or... Agriculture reserves the right to refuse payments of any claim for reward when, in its opinion, collusion...

  10. 36 CFR 262.1 - Rewards in connection with fire or property prosecutions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... grass upon the lands of the United States within the National Forest System or nearby. (2) Not exceeding... kindled or caused to be kindled a fire on lands of the United States within the National Forest System or... Agriculture reserves the right to refuse payments of any claim for reward when, in its opinion, collusion...

  11. 36 CFR 262.1 - Rewards in connection with fire or property prosecutions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... grass upon the lands of the United States within the National Forest System or nearby. (2) Not exceeding... kindled or caused to be kindled a fire on lands of the United States within the National Forest System or... Agriculture reserves the right to refuse payments of any claim for reward when, in its opinion, collusion...

  12. Shift of Circadian Feeding Pattern by High-Fat Diets Is Coincident with Reward Deficits in Obese Mice

    PubMed Central

    Valladolid-Acebes, Ismael; Fole, Alberto; Cano, Victoria; Merino, Beatriz; Stucchi, Paula; Ruggieri, Daniela; López, Laura; Alguacil, Luis Fernando; Ruiz-Gayo, Mariano

    2012-01-01

    Recent studies provide evidence that high-fat diets (HF) trigger both i) a deficit of reward responses linked to a decrease of mesolimbic dopaminergic activity, and ii) a disorganization of circadian feeding behavior that switch from a structured meal-based schedule to a continuous snacking, even during periods normally devoted to rest. This feeding pattern has been shown to be a cause of HF-induced overweight and obesity. Our hypothesis deals with the eventual link between the rewarding properties of food and the circadian distribution of meals. We have investigated the effect of circadian feeding pattern on reward circuits by means of the conditioned-place preference (CPP) paradigm and we have characterized the rewarding properties of natural (food) and artificial (cocaine) reinforcers both in free-feeding ad libitum HF mice and in HF animals submitted to a re-organized feeding schedule based on the standard feeding behavior displayed by mice feeding normal chow (“forced synchronization”). We demonstrate that i) ad libitum HF diet attenuates cocaine and food reward in the CPP protocol, and ii) forced synchronization of feeding prevents this reward deficit. Our study provides further evidence that the rewarding impact of food with low palatability is diminished in mice exposed to a high-fat diet and strongly suggest that the decreased sensitivity to chow as a positive reinforcer triggers a disorganized feeding pattern which might account for metabolic disorders leading to obesity. PMID:22570696

  13. Components and characteristics of the dopamine reward utility signal.

    PubMed

    Stauffer, William R; Lak, Armin; Kobayashi, Shunsuke; Schultz, Wolfram

    2016-06-01

    Rewards are defined by their behavioral functions in learning (positive reinforcement), approach behavior, economic choices, and emotions. Dopamine neurons respond to rewards with two components, similar to higher order sensory and cognitive neurons. The initial, rapid, unselective dopamine detection component reports all salient environmental events irrespective of their reward association. It is highly sensitive to factors related to reward and thus detects a maximal number of potential rewards. It also senses aversive stimuli but reports their physical impact rather than their aversiveness. The second response component processes reward value accurately and starts early enough to prevent confusion with unrewarded stimuli and objects. It codes reward value as a numeric, quantitative utility prediction error, consistent with formal concepts of economic decision theory. Thus, the dopamine reward signal is fast, highly sensitive and appropriate for driving and updating economic decisions. J. Comp. Neurol. 524:1699-1711, 2016. © 2015 Wiley Periodicals, Inc. PMID:26272220

  14. "Small Steps, Big Rewards": Preventing Type 2 Diabetes

    MedlinePlus

    ... please turn Javascript on. Feature: Diabetes "Small Steps, Big Rewards": Preventing Type 2 Diabetes Past Issues / Fall ... These are the plain facts in "Small Steps. Big Rewards: Prevent Type 2 Diabetes," an education campaign ...

  15. Consequences of Adolescent Ethanol Consumption on Risk Preference and Orbitofrontal Cortex Encoding of Reward.

    PubMed

    McMurray, Matthew Stephen; Amodeo, Leslie Renee; Roitman, Jamie Donahey

    2016-04-01

    Critical development of the prefrontal cortex occurs during adolescence, a period of increased independence marked by decision making that often includes engagement in risky behaviors, such as substance use. Consumption of alcohol during adolescence has been associated with increased impulsivity that persists across the lifespan, an effect which may be caused by long-term disruptions in cortical processing of rewards. To determine if alcohol consumption alters cortical encoding of rewards of different sizes and probabilities, we gave rats limited access to alcohol in gelatin during adolescence only. In adulthood, we recorded the electrophysiological activity of individual neurons of the orbitofrontal cortex while rats performed a risk task that varied the level of risk from day-to-day. Rats that had consumed higher levels of alcohol showed increased risk preference in the task compared with control and low alcohol-consuming rats. Patterns of neuronal responses were identified using principal component analysis. Of the multiple patterns observed, only one was modulated by adolescent alcohol consumption and showed strongest modulation after reward receipt. This subpopulation of neurons showed blunted firing rates following rewards in alcohol-consuming rats, suggesting a mechanism through which adolescent alcohol exposure may have lasting effects on reward processing in the context of decision making. The differences in OFC responses between high alcohol consumers and control animals not given access to alcohol support the idea that, regardless of potential variability in innate alcohol preferences, voluntary consumption of alcohol during adolescence biases choice patterns longitudinally through alterations in cortical function. PMID:26370327

  16. Social and monetary reward processing in autism spectrum disorders

    PubMed Central

    2012-01-01

    Background Social motivation theory suggests that deficits in social reward processing underlie social impairments in autism spectrum disorders (ASD). However, the extent to which abnormalities in reward processing generalize to other classes of stimuli remains unresolved. The aim of the current study was to examine if reward processing abnormalities in ASD are specific to social stimuli or can be generalized to other classes of reward. Additionally, we sought to examine the results in the light of behavioral impairments in ASD. Methods Participants performed adapted versions of the social and monetary incentive delay tasks. Data from 21 unmedicated right-handed male participants with ASD and 21 age- and IQ-matched controls were analyzed using a factorial design to examine the blood-oxygen-level-dependent (BOLD) response during the anticipation and receipt of both reward types. Results Behaviorally, the ASD group showed less of a reduction in reaction time (RT) for rewarded compared to unrewarded trials than the control group. In terms of the fMRI results, there were no significant group differences in reward circuitry during reward anticipation. During the receipt of rewards, there was a significant interaction between group and reward type in the left dorsal striatum (DS). The ASD group showed reduced activity in the DS compared to controls for social rewards but not monetary rewards and decreased activation for social rewards compared to monetary rewards. Controls showed no significant difference between the two reward types. Increased activation in the DS during social reward processing was associated with faster response times for rewarded trials, compared to unrewarded trials, in both groups. This is in line with behavioral results indicating that the ASD group showed less of a reduction in RT for rewarded compared to unrewarded trials. Additionally, de-activation to social rewards was associated with increased repetitive behavior in ASD. Conclusions In line

  17. Obesity and the Neurocognitive Basis of Food Reward and the Control of Intake12

    PubMed Central

    Ziauddeen, Hisham; Alonso-Alonso, Miguel; Hill, James O; Kelley, Michael; Khan, Naiman A

    2015-01-01

    With the rising prevalence of obesity, hedonic eating has become an important theme in obesity research. Hedonic eating is thought to be that driven by the reward of food consumption and not metabolic need, and this has focused attention on the brain reward system and how its dysregulation may cause overeating and obesity. Here, we begin by examining the brain reward system and the evidence for its dysregulation in human obesity. We then consider the issue of how individuals are able to control their hedonic eating in the present obesogenic environment and compare 2 contrasting perspectives on the control of hedonic eating, specifically, enhanced control of intake via higher cognitive control and loss of control over intake as captured by the food addiction model. We conclude by considering what these perspectives offer in terms of directions for future research and for potential interventions to improve control over food intake at the population and the individual levels. PMID:26178031

  18. Circadian Mechanisms Underlying Reward-Related Neurophysiology and Synaptic Plasticity.

    PubMed

    Parekh, Puja K; McClung, Colleen A

    2015-01-01

    Evidence from clinical and preclinical research provides an undeniable link between disruptions in the circadian clock and the development of psychiatric diseases, including mood and substance abuse disorders. The molecular clock, which controls daily patterns of physiological and behavioral activity in living organisms, when desynchronized, may exacerbate or precipitate symptoms of psychiatric illness. One of the outstanding questions remaining in this field is that of cause and effect in the relationship between circadian rhythm disruption and psychiatric disease. Focus has recently turned to uncovering the role of circadian proteins beyond the maintenance of homeostatic systems and outside of the suprachiasmatic nucleus (SCN), the master pacemaker region of the brain. In this regard, several groups, including our own, have sought to understand how circadian proteins regulate mechanisms of synaptic plasticity and neurotransmitter signaling in mesocorticolimbic brain regions, which are known to be critically involved in reward processing and mood. This regulation can come in the form of direct transcriptional control of genes central to mood and reward, including those associated with dopaminergic activity in the midbrain. It can also be seen at the circuit level through indirect connections of mesocorticolimbic regions with the SCN. Circadian misalignment paradigms as well as genetic models of circadian disruption have helped to elucidate some of the complex interactions between these systems and neural activity influencing behavior. In this review, we explore findings that link circadian protein function with synaptic adaptations underlying plasticity as it may contribute to the development of mood disorders and addiction. In light of recent advances in technology and sophisticated methods for molecular and circuit-level interrogation, we propose future directions aimed at teasing apart mechanisms through which the circadian system modulates mood and reward

  19. Circadian Mechanisms Underlying Reward-Related Neurophysiology and Synaptic Plasticity

    PubMed Central

    Parekh, Puja K.; McClung, Colleen A.

    2016-01-01

    Evidence from clinical and preclinical research provides an undeniable link between disruptions in the circadian clock and the development of psychiatric diseases, including mood and substance abuse disorders. The molecular clock, which controls daily patterns of physiological and behavioral activity in living organisms, when desynchronized, may exacerbate or precipitate symptoms of psychiatric illness. One of the outstanding questions remaining in this field is that of cause and effect in the relationship between circadian rhythm disruption and psychiatric disease. Focus has recently turned to uncovering the role of circadian proteins beyond the maintenance of homeostatic systems and outside of the suprachiasmatic nucleus (SCN), the master pacemaker region of the brain. In this regard, several groups, including our own, have sought to understand how circadian proteins regulate mechanisms of synaptic plasticity and neurotransmitter signaling in mesocorticolimbic brain regions, which are known to be critically involved in reward processing and mood. This regulation can come in the form of direct transcriptional control of genes central to mood and reward, including those associated with dopaminergic activity in the midbrain. It can also be seen at the circuit level through indirect connections of mesocorticolimbic regions with the SCN. Circadian misalignment paradigms as well as genetic models of circadian disruption have helped to elucidate some of the complex interactions between these systems and neural activity influencing behavior. In this review, we explore findings that link circadian protein function with synaptic adaptations underlying plasticity as it may contribute to the development of mood disorders and addiction. In light of recent advances in technology and sophisticated methods for molecular and circuit-level interrogation, we propose future directions aimed at teasing apart mechanisms through which the circadian system modulates mood and reward

  20. Reward and Toxicity of Cocaine Metabolites Generated by Cocaine Hydrolase.

    PubMed

    Murthy, Vishakantha; Geng, Liyi; Gao, Yang; Zhang, Bin; Miller, Jordan D; Reyes, Santiago; Brimijoin, Stephen

    2015-08-01

    Butyrylcholinesterase (BChE) gene therapy is emerging as a promising concept for treatment of cocaine addiction. BChE levels after gene transfer can rise 1000-fold above those in untreated mice, making this enzyme the second most abundant plasma protein. For months or years, gene transfer of a BChE mutated into a cocaine hydrolase (CocH) can maintain enzyme levels that destroy cocaine within seconds after appearance in the blood stream, allowing little to reach the brain. Rapid enzyme action causes a sharp rise in plasma levels of two cocaine metabolites, benzoic acid (BA) and ecgonine methyl ester (EME), a smooth muscle relaxant that is mildly hypotensive and, at best, only weakly rewarding. The present study, utilizing Balb/c mice, tested reward effects and cardiovascular effects of administering EME and BA together at molar levels equivalent to those generated by a given dose of cocaine. Reward was evaluated by conditioned place preference. In this paradigm, cocaine (20 mg/kg) induced a robust positive response but the equivalent combined dose of EME + BA failed to induce either place preference or aversion. Likewise, mice that had undergone gene transfer with mouse CocH (mCocH) showed no place preference or aversion after repeated treatments with a near-lethal 80 mg/kg cocaine dose. Furthermore, a single administration of that same high cocaine dose failed to affect blood pressure as measured using the noninvasive tail-cuff method. These observations confirm that the drug metabolites generated after CocH gene transfer therapy are safe even after a dose of cocaine that would ordinarily be lethal. PMID:25814464

  1. Encouraging Classroom Participation with Empty Extrinsic Rewards

    ERIC Educational Resources Information Center

    Guinee, William

    2012-01-01

    In this article, the author talks about how to encourage classroom participation with empty extrinsic rewards. He uses "bonus points" in awarding students for particularly interesting or well thought-out contributions to the class discussion. These bonus points have absolutely no effect on the student's course grade. But the students respond…

  2. Parsing Reward and Aversion in the Amygdala.

    PubMed

    Maren, Stephen

    2016-04-20

    The basolateral amygdala (BLA) is critical for encoding the value of stimuli. Beyeler et al. (2016) now show that distinct populations of BLA neurons, which are defined by their efferent targets, code reward and aversion. This arrangement promotes parallel processing of biologically relevant events. PMID:27100192

  3. Motivating Intrapreneurs: The Relevance of Rewards

    ERIC Educational Resources Information Center

    de Villiers-Scheepers, M. J.

    2011-01-01

    A challenge faced by management graduates in promoting intrapreneurship to achieve competitive advantage is the use of motivational techniques that build commitment to entrepreneurial behaviour. Despite the acknowledged importance of rewards to encourage innovation, there is surprisingly little empirical evidence to provide guidance on which…

  4. Rewards of Fostering Children with Disabilities

    ERIC Educational Resources Information Center

    Brown, Jason D.

    2008-01-01

    A random sample of parents fostering children with disabilities in a major Canadian city was asked "what are the rewards you receive from fostering a child with a disability?" A total of 57 unique responses were obtained and grouped together by the foster parents. Two statistical analyses were applied to the grouping data: multidimensional scaling…

  5. Reward Structures in the Public High School

    ERIC Educational Resources Information Center

    Spuck, Dennis W.

    1974-01-01

    Examines the relationship between eight categories of rewards available to teachers in high schools and teacher behaviors of absenteeism, recruitment, and retention. Findings emphasize the importance of intrinsic motivators in professional organizations and suggest basic differences in motivational patterns between professional and production…

  6. Anticipated Reward Enhances Offline Learning during Sleep

    ERIC Educational Resources Information Center

    Fischer, Stefan; Born, Jan

    2009-01-01

    Sleep is known to promote the consolidation of motor memories. In everyday life, typically more than 1 isolated motor skill is acquired at a time, and this possibly gives rise to interference during consolidation. Here, it is shown that reward expectancy determines the amount of sleep-dependent memory consolidation. Subjects were trained on 2…

  7. Revitalizing Faculty Work through Intrinsic Rewards.

    ERIC Educational Resources Information Center

    Froh, Robert C.; And Others

    1993-01-01

    A faculty survey suggests that college climate can help maximize faculty effectiveness. Institutions are making use of the intrinsic rewards of academic work to improve its quality, by helping faculty reach new levels of understanding and mutual learning with students, accomplish greater mastery of content, and find successful new teaching…

  8. Value Orientation, Organizational Rewards, and Job Satisfaction.

    ERIC Educational Resources Information Center

    Cascio, Wayne F.

    The nationwide sales force (N=540) of a large food and beverage firm responded to a mail survey designed to investigate the role of value orientation as a moderator of the relationship between organizational rewards and job satisfaction. Of the two main elements in the investigation, the first was concerned with the predictive efficiency of two…

  9. Functional connectivity in obesity during reward processing.

    PubMed

    García-García, I; Jurado, M A; Garolera, M; Segura, B; Marqués-Iturria, I; Pueyo, R; Vernet-Vernet, M; Sender-Palacios, M J; Sala-Llonch, R; Ariza, M; Narberhaus, A; Junqué, C

    2013-02-01

    Obesity is a health problem that has become a major focus of attention in recent years. There is growing evidence of an association between obesity and differences in reward processing. However, it is not known at present whether these differences are linked exclusively to food, or whether they can be detected in other rewarding stimuli. We compared responses to food, rewarding non-food and neutral pictures in 18 young adults with obesity and 19 normal-weight subjects using independent component analysis. Both groups modulated task-related activity in a plausible way. However, in response to both food and non-food rewarding stimuli, participants with obesity showed weaker connectivity in a network involving activation of frontal and occipital areas and deactivation of the posterior part of the default mode network. In addition, obesity was related with weaker activation of the default mode network and deactivation of frontal and occipital areas while viewing neutral stimuli. Together, our findings suggest that obesity is related to a different allocation of cognitive resources in a fronto-occipital network and in the default mode network. PMID:23103690

  10. 28 CFR 7.2 - Amount of reward.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Amount of reward. 7.2 Section 7.2 Judicial Administration DEPARTMENT OF JUSTICE REWARDS FOR CAPTURE OF ESCAPED FEDERAL PRISONERS § 7.2 Amount of reward. Within the discretion of the Warden or U.S. Marshal concerned, a reward not in excess of $200 may be granted for each capture of...