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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. Attenuation by dextromethorphan on the higher liability to morphine-induced reward, caused by prenatal exposure of morphine in rat offspring.

    PubMed

    Wu, Ling-Yi; Chen, Jain-Fang; Tao, Pao-Luh; Huang, Eagle Yi-Kung

    2009-11-25

    Co-administration of dextromethorphan (DM) with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on morphine-induced reward and behavioral sensitization (possibly related to the potential to induce morphine addiction) in morphine-exposed offspring. Conditioned place preference and locomotor activity tests revealed that the p60 male offspring of chronic morphine-treated female rats were more vulnerable to morphine-induced reward and behavioral sensitization. The administration of a low dose of morphine (1 mg/kg, i.p.) in these male offspring also increased the dopamine and serotonin turnover rates in the nucleus accumbens, which implied that they were more sensitive to morphine. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Thus, DM may possibly have a great potential in the prevention of higher vulnerability to psychological dependence of morphine in the offspring of morphine-addicted mothers.

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

    PubMed

    Nathaniel, Thomas I; Panksepp, Jaak; Huber, Robert

    2009-02-11

    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 2.5 microg/g, 5.0 microg/g and 10.0 microg/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 microg/g, 5.0 microg/g and 10.0 microg/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.

  4. 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.

  5. Potentiation of morphine-induced conditioned place preference with concurrent use of amantadine and fluvoxamine by the intraperitoneal and intracerebroventricular injection in rat.

    PubMed

    Maleki, Saeid Abbasi; Samini, Morteza; Babapour, Vahab; Mehr, Shahram Ejtemaei; Cheraghiyan, Siyamak; Nouri, Mir H Khayat

    2008-07-19

    In this study, the effect of concurrent use of fluvoxamine and amantadine on morphine-induced conditioned place preference (CPP) was investigated by the intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection in rat. The CPP paradigms took place on 6 consecutive days by using an unbiased procedure. Our results showed that i.p. injection of morphine sulfate (2.5-10mg/kg) induced CPP in rat. On day 6, fluvoxamine (5 and 10mg/kg, i.p.), and amantadine (5 and 10mg/kg, i.p.) both increased morphine-induced conditioned place preference. Intracerebroventricular injection of fluvoxamine (10 microg/rat) and amantadine (10 microg/rat) were also increased morphine-induced conditioned preference significantly. Concurrent use of fluvoxamine (5mg/kg, i.p.; 10 microg/rat i.c.v.) and amantadine (10mg/kg, i.p.; 10 microg/rat, i.c.v.) potentiated morphine-induced conditioned preference significantly. Release of dopamine from neurons cause reinforcing behavior. Morphine produces reinforcement (reward) effect by activation of mu receptors which facilitated dopaminergic transmission through dopamine release. Fluvoxamine, a serotonin reuptake inhibitor, increase serotonin concentration in synaptic clefts, which is a potent stimulator of dopamine release. Amantadine also appears to work by increasing dopamine release from neuron. In conclusion, our results show that concurrent use of fluvoxamine and amantadine potentiate morphine-like effect on CPP through increasing dopaminergic transmission and this combination may simulate the rewarding effect of morphine and can be candidate for controlling the drug compulsive seeking in morphine dependent subjects.

  6. 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

  7. Effects of dronabinol on morphine-induced dopamine-related behavioral effects in animals.

    PubMed

    Mori, Tomohisa; Shibasaki, Masahiro; Abe, Minako; Udagawa, Yuya; Suzuki, Tsutomu

    2012-11-01

    The present study examined the effects of dronabinol, a United States FDA-approved synthetic cannabinoid receptor agonist, on morphine (a prototypic μ-opioid receptor agonist)-induced dopamine-related behaviors in animals. Dronabinol suppressed the rewarding effects of morphine in rats and its emetic effects in ferrets. Furthermore, the morphine-induced increase in dopamine release from the nucleus accumbens was significantly attenuated by dronabinol, which indicated that the suppressive effects of dronabinol on morphine-induced behaviors are at least in part mediated by regulation of the dopaminergic system. Since cannabinoid receptor agonists have been shown to enhance the antinociceptive effects of morphine, the use of dronabinol as an adjuvant could be useful for preventing the adverse effects of μ-opioid receptor agonists when used to control pain.

  8. Morphine induces albuminuria by compromising podocyte integrity.

    PubMed

    Lan, Xiqian; Rai, Partab; Chandel, Nirupama; Cheng, Kang; Lederman, Rivka; Saleem, Moin A; Mathieson, Peter W; Husain, Mohammad; Crosson, John T; Gupta, Kalpna; Malhotra, Ashwani; Singhal, Pravin C

    2013-01-01

    Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD), the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for immunohistochemical studies and Western blot. For in vitro studies, human podocytes were treated with morphine and then probed for the molecular markers of slit diaphragm. Morphine-receiving mice displayed a significant increase in albuminuria and showed effacement of podocyte foot processes. In both in vivo and in vitro studies, the expression of synaptopodin, a molecular marker for podocyte integrity, and the slit diaphragm constituting molecules (SDCM), such as nephrin, podocin, and CD2-associated protein (CD2AP), were decreased in morphine-treated podocytes. In vitro studies indicated that morphine modulated podocyte expression of SDCM through opiate mu (MOR) and kappa (KOR) receptors. Since morphine also enhanced podocyte oxidative stress, the latter seems to contribute to decreased SDCM expression. In addition, AKT, p38, and JNK pathways were involved in morphine-induced down regulation of SDCM in human podocytes. These findings demonstrate that morphine has the potential to alter the glomerular filtration barrier by compromising the integrity of podocytes.

  9. 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.

  10. 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.

  11. Comparing of the Effects of Hypericin and Synthetic Antidepressants on the Expression of Morphine-Induced Conditioned Place Preference

    PubMed Central

    Assadi, Assad; Zarrindast, Mohammad Reza; Jouyban, Abolghasem; Samini, Morteza

    2011-01-01

    The effect of hypericin on the expression of morphine-induced conditioned place preference (CPP) was investigated and compared with the effect of the synthetic antidepressants. The CPP paradigms took place over six days using an unbiased procedure. The results demonstrate that intra-peritoneal (IP) injection of morphine sulfate (2.5, 5 and 10 mg/Kg) significantly induce the CPP in rat. Intra-peritoneal and intracerebroventricular (ICV) injection of hypericin and/or synthetic antidepressants augmented morphine-induced CPP. It has been suggested that the adrenergic, serotonergic and dopaminergic neurotransmissions play an important role in mediating the antidepressant effect of hypericin and this effect may be due to its inhibitory effect on the reuptake of neurotransmitters. Morphine produces a reinforcement (reward) effect by activating. The μ-receptors that facilitate dopaminergic transmission. Serotonin is also a potent stimulator of dopamine release in such a way that an increase in brain serotonin could possibly stimulate the dopaminergic system. In conclusion, it may suggest that the augmentation of morphine-induced CPP by hypericin and synthetic antidepressants may be related to the increasing dopamine and serotonin concentrations in synaptic clefts. PMID:24250400

  12. Morphine-Induced Constipation Develops With Increased Aquaporin-3 Expression in the Colon via Increased Serotonin Secretion.

    PubMed

    Kon, Risako; Ikarashi, Nobutomo; Hayakawa, Akio; Haga, Yusuke; Fueki, Aika; Kusunoki, Yoshiki; Tajima, Masataka; Ochiai, Wataru; Machida, Yoshiaki; Sugiyama, Kiyoshi

    2015-06-01

    Aquaporin-3 (AQP3) is a water channel that is predominantly expressed in the colon, where it plays a critical role in the regulation of fecal water content. This study investigated the role of AQP3 in the colon in morphine-induced constipation. AQP3 expression levels in the colon were analyzed after oral morphine administration to rats. The degree of constipation was analyzed after the combined administration of HgCl(2) (AQP3 inhibitor) or fluoxetine (5-HT reuptake transporter [SERT] inhibitor) and morphine. The mechanism by which morphine increased AQP3 expression was examined in HT-29 cells. AQP3 expression levels in rat colon were increased during morphine-induced constipation. The combination of HgCl(2) and morphine improved morphine-induced constipation. Treatment with morphine in HT-29 cells did not change AQP3 expression. However, 5-HT treatment significantly increased the AQP3 expression level and the nuclear translocation of peroxisome proliferator-activated receptor gamma (PPARγ) 1 h after treatment. Pretreatment with fluoxetine significantly suppressed these increases. Fluoxetine pretreatment suppressed the development of morphine-induced constipation and the associated increase in AQP3 expression in the colon. The results suggest that morphine increases the AQP3 expression level in the colon, which promotes water absorption from the luminal side to the vascular side and causes constipation. This study also showed that morphine-induced 5-HT secreted from the colon was taken into cells by SERT and activated PPARγ, which subsequently increased AQP3 expression levels.

  13. 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.

  14. The possible role of medial prefrontal cortex beta-1-adrenoceptors in morphine-induced amnesia.

    PubMed

    Torkaman-Boutorabi, Anahita; Hashemi-Hezaveh, Seyed-Milad; Sheidadoust, Hadi; Zarrindast, Mohammad-Reza

    2014-01-01

    The prelimbic region of the medial prefrontal cortex (mPFC) in the brain is crucial for memory. Norepinephrine elicits an important influence on mPFC functions. The stimulation of β-adrenoceptors (β-ARs) may play a critical role in the consolidation of long-term memory. The present study examines the possible role of β₁-ARs located in the mPFC on morphine-induced amnesia in rats. The animals were bilaterally implanted with chronic cannulas in the mPFC, trained in a step-through-type passive avoidance task and tested 24 h after training to measure step-through latency. Our present results indicated that posttraining intraperitoneal administration of morphine (2.5, 5 and 7.5 mg/kg) dose-dependently reduced the step-through latency. Different doses of xamoterol (0.01, 0.1 and 1 µg/rat) have shown no significant change in the step-through latency, but posttraining intra-mPFC microinjection of atenolol (0.2 and 0.4 µg/rat) had an amnesic effect. Moreover, atenolol-caused amnesia was reversed by an ineffective dose of xamoterol (0.1 µg/rat). On the other hand, coadministration of an ineffective dose of atenolol (0.1 µg/rat) with an ineffective dose of morphine (2.5 mg/kg) induced an amnesic effect. Meanwhile, xamoterol had no effect on morphine-induced amnesia. These results suggest that β₁-ARs of the prelimbic region in the mPFC may play an important role in morphine-induced amnesia.

  15. Reward-seeking behavior and addiction: cause or cog?

    PubMed

    Arias-Carrión, Oscar; Salama, Mohamed

    2012-09-01

    Although dopaminergic system represents the cornerstone in rewarding, other neurotransmitters can modulate both the reward system and the psychomotor effects of addictive drugs. Many hypotheses have been proposed for a better understanding of the reward system and its role in drug addiction. However, after many years of investigation, no single theory can completely explain the neural basis of drug addiction. Recent reports introduce novel neurotransmitters into the game e.g. dynorphins, orexins, histamine, gheralin and galanin. The interacting functions of these neurotransmitters have shown that the reward system and its role in drug dependence, is far more complicated than was thought before. Individual variations exist regarding response to drug exposure, vulnerability for addiction and the effects of different cues on reward systems. Consequently, genetic variations of neurotransmission are thought to influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. However, the individual variations can not be based mainly on genetics; environmental factors seem to play a role too. Here we discuss the current knowledge about the orquestic regulation of different neurotransmitters on reward-seeking behavior and their potential effect on drug addiction.

  16. 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

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

    PubMed

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

    2015-11-05

    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.

  18. Saffron (Crocus sativus) ethanolic extract and its constituent, safranal, inhibits morphine-induced place preference in mice.

    PubMed

    Ghoshooni, H; Daryaafzoon, M; Sadeghi-Gharjehdagi, S; Zardooz, H; Sahraei, H; Tehrani, S P; Noroozzadeh, A; Bahrami-Shenasfandi, F; Kaka, G H; Sadraei, S H

    2011-10-15

    The effects of saffron ethanolic extract and its constituent, safranal, on the acquisition and expression of morphine-induced place preference (CPP) in male Swiss Webster mice (20-25 g) were investigated in the present study. An unbiased place conditioning method was applied for assessment of morphine reward properties. The saffron extract and safranal were administered intraperitoneally (i.p.) during (acquisition) or after induction (expression) of morphine CPP. In a pilot study, the extract and safranal were alone administered to the animals to assess if they have any reward properties. Subcutaneous (s.c.) of morphine (4 and 8 mg kg(-1)) and extract (50 mg kg(-1); i.p.) induced CPP. Extract (10, 50 and 100 mg kg(-1); i.p.) reduced the acquisition and expression of morphine CPP. The same results were obtained when safranal (1, 5 and 10 mg kg(-1), i.p.) was used. It may be concluded that both ethanolic saffron extract and safranal can inhibit the acquisition and expression of morphine-induced CPP in the mice.

  19. A mechanism of action for morphine-induced immunosuppression: corticosterone mediates morphine-induced suppression of natural killer cell activity.

    PubMed

    Freier, D O; Fuchs, B A

    1994-09-01

    Morphine is a drug of abuse with an ability to down-regulate immune responsiveness that could have potentially serious consequences in both heroin addicts and in the clinical environment. The exact mechanism of action by which morphine induces immunosuppression has yet to be clearly determined. A direct mechanism of action is suggested to operate through lymphocyte opiate receptors, but the nature of such receptors is still in question. The alternative, an indirect mechanism of action is proposed to be mediated by two possible pathways, hypothalamic-pituitary-adrenal axis activation with increased production of adrenal corticosteroids, or activation of the sympathetic nervous system and concomitant catecholamine release. Natural killer (NK) cell activity was used to determine potential indirect mechanisms of action for morphine. NK activity in the B6C3F1 mouse was suppressed between 12 and 48 hr after implantation of 75 mg timed-release morphine pellets. Morphine suppressed NK activity in a dose-responsive manner. The opiate antagonists naloxone and naltrexone completely blocked morphine-induced suppression of NK activity, whereas naloxone methiodide, a congener that crosses the blood-brain barrier much more slowly than naloxone, produced very little blockade. Implantation of the 75-mg morphine pellets produced a significant elevation in serum corticosterone levels. In vitro exposure to corticosterone is known to suppress NK activity directly, whereas in vitro morphine was unable to alter directly NK activity. The glucocorticoid receptor antagonist Roussel-Uclaf 38486 blocked morphine-induced suppression of NK activity in a dose-responsive fashion. Naltrexone (10-mg pellet) antagonized the morphine-induced elevation in serum corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Repeated administration of dopaminergic agents in the dorsal hippocampus and morphine-induced place preference.

    PubMed

    Zarrindast, M-R; Nasehi, M; Rostami, P; Rezayof, A; Fazli-Tabaei, S

    2005-03-01

    The aim of the present experiments was to investigate whether repeated intra-hippocampal CA1 (intra-CA1) administration of dopaminergic agents can affect morphine-induced conditioned place preference (CPP). Effects of repeated intra-CA1 injections of dopamine (DA) receptor agonists and antagonists on morphine-induced CPP in rats were investigated using an unbiased 3-day schedule of place conditioning. Animals receiving once-daily subcutaneous (s.c.) injections of morphine (1-9 mg/kg) or saline (1.0 ml/kg, s.c.) showed a significant place preference in a dose-dependent manner: the maximum response was observed with 3 mg/kg morphine. Three days' intra-CA1 injections of apomorphine (0.25-1 microg/rat) followed by 5 days free of the drug, significantly decreased morphine CPP (1 and 3 mg/kg, s.c.). Moreover, pre-treatment with the highest dose of apomorphine (1 microg/rat) altered the effect of morphine to an aversive response. The morphine (1 and 3 mg/kg) CPP was also significantly decreased in animals that previously received three intra-CA1 injections of SKF 38393 (2-9 microg/rat), quinpirole (1-3 microg/rat) or sulpiride (1-3 microg/rat), and significantly increased in animals that had previously received three intra-CA1 injections of SCH 23390 (0.02 microg/rat). The 3-day pre-treatment with apomorphine, SKF 38393 or quinpirole reduced locomotor activity in the test session, while SCH 23390 and sulpiride did not have any influence on locomotor activity. It is concluded that repeated injections of DA receptor agents in the dorsal hippocampus, followed by 5 days free of the drugs, can affect morphine reward.

  1. Effects of the fruit essential oil of Cuminum cyminum L. on the acquisition and expression of morphine-induced conditioned place preference in mice.

    PubMed

    Khatibi, Ali; Haghparast, Abbas; Shams, Jamal; Dianati, Elham; Komaki, Alireza; Kamalinejad, Mohammad

    2008-12-19

    Rewarding properties of opioids are now accepted and widely discussed. These properties can lead to long-term usage of these substances. The main purpose of this study was to investigate the effects of Cuminum cyminum fruit essential oil (FEO) on the acquisition and expression of morphine-induced conditioned place preference (CPP) in mice. CPP was induced by subcutaneous (s.c.) injection of morphine (5mg/kg) in 3 days conditioning schedule. Intraperitoneal (i.p.) administration of Cumin FEO (0.001%, 0.01%, 0.1%, 0.5%, 1% and 2%; 5 ml/kg) or Tween-80 (0.5%; 5 ml/kg) did not show any conditioning effects. Administration of Cumin FEO (0.001-2%; 5 ml/kg; i.p.), 60 min before test on day 5 (expression) decreased the conditioning scores at the doses of 1% and 2% while i.p. injection of Cumin FEO (0.001-2%; 5 ml/kg), 60 min before morphine injection (5mg/kg; s.c.) during 3 days of conditioning session (acquisition) significantly resulted in decrement of rewarding properties of morphine at the doses of 0.1%, 0.5%, 1% and 2% in dose-dependent manner. Tween-80 as a vehicle did not suppress the acquisition and expression of morphine-induced CPP. The results showed that the C. cyminum fruit essential oil reduces the acquisition and expression of morphine-induced conditioned place preference in mice.

  2. 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.

  3. 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.

  4. 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.

  5. Differentiation state affects morphine induced cell regulation in neuroblastoma cultured cells.

    PubMed

    Fiore, Giovina; Ghelardini, Carla; Bruni, Giancarlo; Guarna, Massimo; Bianchi, Enrica

    2013-10-25

    Neuroblastoma (NB) is the most common extracranial solid cancer in childhood and the most common cancer in infancy. Our purpose was to investigate in vitro how cancer cell survival occurs in presence of morphine in undifferentiated and differentiated SHSY-5Y human neuroblastoma cultured cell line. Exposure of differentiated cells to morphine dose-dependently induced apoptosis in these cells through c-Jun N-terminal kinase (JNK)/caspase pathway. Otherwise, morphine induced activation for mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, caused positive regulation of cell survival in undifferentiated cells. Therefore, cell differentiation state bimodally affects the cellular regulation activity triggered by morphine in isolated cultured neuroblastoma cells raising concerns about the application of morphine to this type of cancer patients.

  6. 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.

  7. Morphine Induces Ubiquitin-Proteasome Activity and Glutamate Transporter Degradation*

    PubMed Central

    Yang, Liling; Wang, Shuxing; Sung, Backil; Lim, Grewo; Mao, Jianren

    2008-01-01

    Glutamate transporters play a crucial role in physiological glutamate homeostasis, neurotoxicity, and glutamatergic regulation of opioid tolerance. However, how the glutamate transporter turnover is regulated remains poorly understood. Here we show that chronic morphine exposure induced posttranscriptional down-regulation of the glutamate transporter EAAC1 in C6 glioma cells with a concurrent decrease in glutamate uptake and increase in proteasome activity, which were blocked by the selective proteasome inhibitor MG-132 or lactacystin but not the lysosomal inhibitor chloroquin. At the cellular level, chronic morphine induced the PTEN (phosphatase and tensin homolog deleted on chromosome Ten)-mediated up-regulation of the ubiquitin E3 ligase Nedd4 via cAMP/protein kinase A signaling, leading to EAAC1 ubiquitination and proteasomal degradation. Either Nedd4 or PTEN knockdown with small interfering RNA prevented the morphine-induced EAAC1 degradation and decreased glutamate uptake. These data indicate that cAMP/protein kinase A signaling serves as an intracellular regulator upstream to the activation of the PTEN/Nedd4-mediated ubiquitin-proteasome system activity that is critical for glutamate transporter turnover. Under an in vivo condition, chronic morphine exposure also induced posttranscriptional down-regulation of the glutamate transporter EAAC1, which was prevented by MG-132, and transcriptional up-regulation of PTEN and Nedd4 within the spinal cord dorsal horn. Thus, inhibition of the ubiquitin-proteasome-mediated glutamate transporter degradation may be an important mechanism for preventing glutamate overexcitation and may offer a new strategy for treating certain neurological disorders and improving opioid therapy in chronic pain management. PMID:18539596

  8. BDNF parabrachio-amygdaloid pathway in morphine-induced analgesia.

    PubMed

    Sarhan, Maysa; Pawlowski, Sophie Anne; Barthas, Florent; Yalcin, Ipek; Kaufling, Jennifer; Dardente, Hugues; Zachariou, Venetia; Dileone, Ralph Joseph; Barrot, Michel; Veinante, Pierre

    2013-08-01

    In addition to its neurotrophic role, brain-derived neurotrophic factor (BDNF) is involved in a wide array of functions, including anxiety and pain. The central amygdaloid nucleus (CeA) contains a high concentration of BDNF in terminals, originating from the pontine parabrachial nucleus. Since the spino-parabrachio-amygdaloid neural pathway is known to convey nociceptive information, we hypothesized a possible involvement of BDNF in supraspinal pain-related processes. To test this hypothesis, we generated localized deletion of BDNF in the parabrachial nucleus using local bilateral injections of adeno-associated viruses in adult floxed-BDNF mice. Basal thresholds of thermal and mechanical nociceptive responses were not altered by BDNF loss and no behavioural deficit was noticed in anxiety and motor tests. However, BDNF-deleted animals displayed a major decrease in the analgesic effect of morphine. In addition, intra-CeA injections of the BDNF scavenger TrkB-Fc in control mice also decreased morphine-induced analgesia. Finally, the number of c-Fos immunoreactive nuclei after acute morphine injection was decreased by 45% in the extended amygdala of BDNF-deleted animals. The absence of BDNF in the parabrachial nucleus thus altered the parabrachio-amygdaloid pathway. Overall, our study provides evidence that BDNF produced in the parabrachial nucleus modulates the functions of the parabrachio-amygdaloid pathway in opiate analgesia.

  9. Diet-induced obesity causes ghrelin resistance in reward processing tasks.

    PubMed

    Lockie, Sarah H; Dinan, Tara; Lawrence, Andrew J; Spencer, Sarah J; Andrews, Zane B

    2015-12-01

    Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing.

  10. Blockade of dorsal hippocampal orexin-1 receptors impaired morphine-induced state-dependent learning.

    PubMed

    Farahmandfar, Maryam; Kadivar, Mehdi; Rastipisheh, Sareh

    2016-12-01

    Behavioral abnormalities associated with opiate addiction include memory and learning deficits, which are the result of some alterations in the neuromodulatory systems. Recently, orexin has shown to influence drug addiction neural circuitry, specifically in mediating reward-related perception and memory. To explore the possible interaction of orexinergic and opioidergic system on modulation of learning and memory, we have investigated the effects of intra-dorsal hippocampal (intra-CA1) administration of orexin-1 receptor agonist and the competitive orexin-1 antagonist, SB-334867, on morphine-induced memory impairment by using step-down passive avoidance task in mice. Pre-training injection of morphine (5mg/kg, i.p.) impaired memory, which was restored when 24h later the same dose of the drug was administered. Pre-test administration of orexin-1 (0.5, 5 and 50pmol, intra-CA1) had not a significant effect on the retention latency compared to the saline-treated animals, but it restored the memory impairment induced by pre-training morphine (5mg/kg, i.p.). Pre-test administration of SB-334867 (10, 20 and 40nmol, intra-CA1) by itself decreased the retention latencies of passive avoidance task. Co-administration of orexin-1 (0.5, 5 and 50pmol, intra-CA1) and morphine (1mg/kg, i.p.) on the test day induced morphine state-dependent memory. Conversely, pre-test injection of SB-334867 (10, 20 and 40nmol, intra-CA1) inhibited the orexin-1-induced potentiation of morphine state-dependent learning on the test day. It is concluded that dorsal hippocampal orexin-1 receptors may be involved, at least in part, in morphine state-dependent learning in mice.

  11. Activating Autophagy in Hippocampal Cells Alleviates the Morphine-Induced Memory Impairment.

    PubMed

    Pan, Jingrui; He, Lei; Li, Xiangpen; Li, Mei; Zhang, Xiaoni; Venesky, Jacob; Li, Yi; Peng, Ying

    2017-04-01

    Morphine abuse in treating severe and chronic pain has become a worldwide problem. But, chronic morphine exposure can cause memory impairment with its mechanisms not fully elucidated by past research sstudies which all focused on the harmful effects of morphine. Autophagy is an important pathway for cells to maintain survival. Here we showed that repeated morphine injection into C57BL/6 mice at a dose of 15 mg/kg per day for 7 days activated autophagic flux mainly in the hippocampi, especially in neurons of hippocampal CA1 region and microglia, with spatial memory impairment confirmed by Morris water maze test. Autophagy inhibition by 3-methyladenine obviously aggravates this morphine-induced memory impairment, accompanied with increased cell deaths in stratum pyramidale of hippocampal CA1, CA3, and DG regions and the activation of microglia to induce inflammation in hippocampus, such as upregulated expression of TNF-α, IL-1β, IL-6, and iNOS, as well as NF-κB' s activation, while morphine alone promoted microglial immunosuppression in hippocampus with autophagy activation which was also confirmed in primary microglia. Taken together, our data indicates that autophagy activating in hippocampal cells can alleviate the memory impairment caused by morphine, by decreasing neuronal deaths in hippocampus and suppressing inflammation in hippocampal microglia, implying that modulating the activation of autophagy might be a promising method to prevent or treat the memory impairment caused by morphine.

  12. Morphine-induced conditioned taste aversions: assessment of sexual dimorphism.

    PubMed

    Randall-Thompson, Jovita F; Riley, Anthony L

    2003-09-01

    Although sex differences in taste aversions have been reported with emetics such as lithium chloride (LiCl), little is known whether such findings generalize to other aversion-inducing drugs, including recreational compounds. One particular class of recreational compounds that induces taste aversions but that has not been examined for sex differences in its aversive properties is the opioids. To assess sex differences in the aversive properties of the opioids, Experiment 1 examined the acquisition and extinction of morphine-induced taste aversions in male and female rats. To determine whether the specific parametric conditions used in Experiment 1 would support sex differences in general, Experiment 2 examined possible sex differences in the acquisition and extinction of LiCl-induced taste aversions, a compound for which sex differences have been previously reported. During acquisition, male and female rats were given 20-min access to a novel saccharin solution and injected with either morphine (0, 10, 18 and 32 mg/kg s.c.; Experiment 1) or LiCl (0, 0.3, 0.6 and 1.2 mEq s.c.; Experiment 2) every fourth day for a total of four conditioning trials. During extinction, subjects were allowed access to saccharin but were not injected (for a total of eight trials). There were no sex differences in acquisition with either morphine or LiCl. There were also no sex differences in extinction with morphine; however, sex differences were found with LiCl, an effect consistent with prior assessments with this drug. The basis for and implications of the differences in the effects of sex on morphine- and LiCl-induced taste aversions were discussed.

  13. Effect of delta 9-tetrahydrocannabinol on the morphine-induced hyperactivity of mice.

    PubMed

    Ulkü, E; Ayhan, I H; Tulunay, F C; Uran, B; Kaymakçalan, S

    1980-01-01

    The effect of delta 9-tetrahydrocannabinol (THC) on the locomotor activity-stimulating action of morphine has been investigated in mice. THC (10 mg/kg) has been found to potentiate morphine-induced hyperactivity. On the other hand, the stimulating action of morphine on motor activity strongly diminished in mice rendered tolerant by the implantation of a morphine pellet. The pretreatment of morphine-tolerant mice with the same dose of THC did not change the effect of morphine on the motor activity. These results suggest that tolerance also developed to the potentiating action of THC on morphine-induced hyperactivity during the development of tolerance to this action of morphine.

  14. Central amygdala nicotinic and 5-HT1A receptors mediate the reversal effect of nicotine and MDMA on morphine-induced amnesia.

    PubMed

    Tirgar, F; Rezayof, A; Zarrindast, M-R

    2014-09-26

    The present study was designed to investigate possible involvement of the central amygdala (CeA) nicotinic acetylcholine (nACh) and 5-hydroxytryptamine 1A (5-HT1A) receptors in the reversal effect of nicotine and 3,4-methylenedioxy-N-methylamphetamine (MDMA or ecstasy) on morphine-induced amnesia. Two guide cannulas were stereotaxically implanted in the CeA regions and a step-through passive avoidance task was used for the assessment of memory retrieval in adult male Wistar rats. Our results indicated that post-training s.c. administration of morphine (3-7-mg/kg) impaired memory retrieval. Pre-test administration of nicotine (0.3- and 0.5-mg/kg, s.c.) reversed morphine-induced amnesia. In addition, pre-test intra-CeA injection of MDMA (1-2-μg/rat) with an ineffective dose of nicotine (0.1-mg/kg, s.c.) improved memory retrieval, suggesting the interactive effect of the drugs on memory formation. It should be noted that that pre-test intra-CeA injection of 2-μg/rat of MDMA by itself produced amnesia. Interestingly, pre-test intra-CeA injection of mecamylamine, a nACh receptor antagonist (1-2-μg/rat) or (S)-WAY 100135 (0.25-1-μg/rat), a selective 5-HT1A receptor antagonist inhibited the improvement of morphine-induced amnesia which was produced by pre-test co-injection of nicotine and MDMA. Pre-test intra-CeA injection of the same doses of MDMA, mecamylamine or (S)-WAY 100135 by itself had no effect on morphine-induced amnesia. Moreover, pre-test injection of the same doses of mecamylamine or (S)-WAY 100135 into the CeA alone could not change memory retrieval. Taken together, it can be concluded that there is a functional interaction between morphine, nicotine and MDMA via the CeA nicotinic and serotonergic receptor mechanisms in passive avoidance memory retrieval. Moreover, cross state-dependent memory retrieval may have been induced between the drugs and this probably depends on the rewarding effects of the drugs.

  15. Involvement of AMPA/Kainate Glutamate Receptor in the Extinction and Reinstatement of Morphine-Induced Conditioned Place Preference: A Behavioral and Molecular Study.

    PubMed

    Siahposht-Khachaki, Ali; Fatahi, Zahra; Yans, Asal; Khodagholi, Fariba; Haghparast, Abbas

    2017-03-01

    Glutamate receptors in mesolimbic areas such as the nucleus accumbens, ventral tegmental area, prefrontal cortex (PFC), and hippocampus (HIP) are a component of the mechanisms of drug-induced reward and can modulate the firing pattern of dopaminergic neurons in the reward system. In addition, several lines of study have indicated that cAMP response element-binding protein (CREB) and c-fos have important role in morphine-induced conditioned place preference (CPP) induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated CREB (p-CREB) and c-fos induction within the nucleus accumbens (NAc), HIP, and PFC after intracerebroventricular (ICV) administration of different doses of CNQX or vehicle during extinction period or reinstatement of morphine-induced CPP. In all groups, the CPP procedure was done; afterward, the conditioning scores were recorded by Ethovision software. After behavioral test recording, we dissected out the NAc, HIP, and PFC regions and measured the p-CREB/CREB ratio and c-fos level by Western blot analysis. Our results showed that administration of CNQX significantly shortened the extinction of morphine CPP. Besides, ICV microinjection of CNQX following extinction period decreased the reinstatement of morphine CPP in extinguished rats. In molecular section, in treatment group, all mentioned factors were dose-dependently decreased in comparison with vehicle group (DMSO) after ICV microinjection of different doses of CNQX but not in pre-extinction microinjection. These findings suggested that antagonism of AMPA receptor decreased p-CREB/CREB ratio and c-fos level in the PFC, NAc, and HIP. Modulation of the drug memory reconsolidation may be useful for faster extinction of drug-induced reward and attenuation of drug-seeking behavior.

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

    PubMed

    Haji, Akira; Kimura, Satoko; Ohi, Yoshiaki

    2016-06-05

    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.

  17. Contributions of spinal D-amino acid oxidase to chronic morphine-induced hyperalgesia.

    PubMed

    Ma, Shuai; Li, Xin-Yan; Gong, Nian; Wang, Yong-Xiang

    2015-12-10

    Spinal D-amino acid oxidase (DAAO) is an FAD-dependent peroxisomal flavoenzyme which mediates the conversion of neutral and polar D-amino acids (including D-serine) to the corresponding α-keto acids, and simultaneously produces hydrogen peroxide and ammonia. This study has aimed to explore the potential contributions of spinal DAAO and its mediated hydrogen peroxide/D-serine metabolism to the development of morphine-induced hyperalgesia. Bi-daily subcutaneous injections of morphine to mice over 7 days induced thermal hyperalgesia as measured by both the hot-plate and tail-immersion tests, and spinal astroglial activation with increased spinal gene expression of DAAO, glial fibrillary acidic protein (GFAP) and pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)). Subcutaneous injections of the potent DAAO inhibitor CBIO (5-chloro-benzo[D]isoxazol-3-ol) prevented and reversed the chronic morphine-induced hyperalgesia. CBIO also inhibited both astrocyte activation and the expression of pro-inflammatory cytokines. Intrathecal injection of the hydrogen peroxide scavenger PBN (phenyl-N-tert-butylnitrone) and of catalase completely reversed established morphine hyperalgesia, whereas subcutaneous injections of exogenous D-serine failed to alter chronic morphine-induced hyperalgesia. These results provided evidence that spinal DAAO and its subsequent production of hydrogen peroxide rather than the D-serine metabolism contributed to the development of morphine-induced hyperalgesia.

  18. 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

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

    PubMed

    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.

  20. Morphine-induced nitric oxide production in isolated, iris-ciliary bodies

    PubMed Central

    Dortch-Carnes, Juanita; Randall, Karen Russell

    2009-01-01

    Considerable evidence suggests that the nitric oxide (NO)/cGMP signaling pathway plays an integral role in opioid receptor-mediated responses in the cardiovascular and immune systems. Previous studies in our laboratory and others have shown that nitric oxide (NO) plays a role in morphine-induced reduction of intraocular pressure (IOP) and pupil diameter (PD) in the New Zealand white (NZW) rabbit. The present study is designed to determine the effect of morphine on NO production in the isolated, iris-ciliary body (ICB), site of aqueous humor production, as this effect could be associated with morphine-stimulated changes in aqueous humor dynamics and iris function. ICBs obtained from normal NZW rabbits were utilized in these experiments. In some experiments, ICB samples were treated with morphine (1, 10 and 100 μM) for 1 hour and later examined for changes in NO levels using a NO detection kit. In other experiments, tissue samples were pretreated with naloxone (non-selective opioid receptor antagonist), L-NAME (non-selective NO synthase inhibitor) or GSH (sulfhydryl reagent) for 30 minutes, followed by treatment with morphine (10 μM). Morphine caused a concentration-dependent increase in the release of NO from ICBs. Levels of NO detected in the incubation medium of ICB samples increased from 1.49 ± 0.19 (control) to 8.81 ± 2.20 μM/mg protein (morphine treated; 100 μM). Morphine-stimulated release of NO was significantly inhibited in tissues pretreated with 10 μM naloxone, L-NAME, or GSH. Results obtained from this study suggest that morphine stimulates NO release from the ICB through a mechanism that involves activation of NO-releasing opioid receptors. These results support the in vivo effects of morphine demonstrated in previous studies. PMID:19555685

  1. Effect of dietary fiber on morphine-induced constipation in rats.

    PubMed

    Niwa, Takashi; Nakao, Makoto; Hoshi, Seiko; Yamada, Kiyofumi; Inagaki, Kazuhiro; Nishida, Mikio; Nabeshima, Toshitaka

    2002-06-01

    Morphine is used to alleviate chronic cancer pain. However, constipation is a major adverse effect that often detracts from the patient's quality of life. In this study, we investigated the effectiveness of dietary fiber on morphine-induced constipation. Rats were fed on a normal diet or one containing either 10% or 20% apple fiber for two weeks before morphine was administered. In the control diet group, the fecal number and dry weight were decreased by treating with morphine in a dose-dependent manner. Moreover, the motility of the small and large intestines was reduced. The fecal number and weight were increased and the colon motility was promoted by dietary fiber, regardless of whether morphine was being administered. The dietary fiber increased the concentration of short-chain fatty acids (SCFAs) in the cecum. These results suggest that dietary fiber has a preventative effect on morphine-induced constipation by increasing SCFAs in the cecum, and thereby promoting colon motility in rats.

  2. Glutamate transporter type 3 participates in maintaining morphine-induced conditioned place preference.

    PubMed

    Wan, Li; Bi, Jiangjiang; Li, Jun; Zuo, Zhiyi

    2017-03-06

    Glutamate transporters (EAAT) have been implicated in the drug addiction behavior. We determined whether EAAT type 3 (EAAT3) played a role in morphine addiction. Six- to eight-week-old EAAT3 knockout (EAAT3(-/-)) mice and their wild-type littermates received 3 intraperitoneal injections of 10mg/kg morphine, each on an alternative day, to induce conditioned place preference (CPP). Two days after the place preference returned to baseline, mice received 2.5mg/kg morphine to induce reinstatement. Some mice received intraperitoneal injection of 4mg/kg riluzole, an EAAT activator, 30min before morphine or saline injection. Hippocampus, medial prefrontal cortex, nucleus accumbens and ventral tegmental area were harvested for Western analysis 24h after the last dose of morphine was injected. Morphine induced CPP in wild-type and EAAT3(-/-) mice. Gender is not a statistically significant factor to influence this behavior. This conditioned behavior extinguished after morphine administration was stopped for 8-9days in wild-type mice, while this extinction occurred 6days after discontinuation of morphine injection in EAAT3(-/-) mice. A small dose of morphine similarly reinstated the conditioned behavior in the wild-type and EAAT3(-/-) mice. Riluzole abolished morphine-induced CPP during the initial place preference. Morphine increased EAAT3 expression in the plasma membrane of medial prefrontal cortex, nucleus accumbens and ventral tegmental area but did not affect EAAT3 expression in the hippocampus. These results suggest that EAAT3 delays the extinction of morphine-induced CPP. EAAT activation may prevent the formation of morphine-induced CPP.

  3. Prepubertal Fischer 344 rats display stronger morphine-induced taste avoidance than prepubertal Lewis rats.

    PubMed

    Hurwitz, Zachary E; Cobuzzi, Jennifer L; Merluzzi, Andrew P; Wetzell, Bradley; Riley, Anthony L

    2014-07-01

    The present report asked if the previously reported differences in morphine-induced conditioned taste avoidance between adult F344 and LEW rats (F344 > LEW) are also evident in prepubescence (early adolescence). To assess this possibility, adult (Experiment 1) and prepubertal (Experiment 2) F344 and LEW rats were assessed for their ability to acquire morphine-induced taste avoidance (0, 3.2, 10, or 18 mg/kg) in a modified taste avoidance procedure. In each experiment, rats of both strains were given repeated pairings of saccharin and morphine followed by a final two-bottle avoidance test. Adult and prepubertal F344 subjects displayed a more rapid acquisition of the avoidance response as well as stronger suppression of consumption than their LEW counterparts. These data suggest the strains differ in their sensitivity to the aversive effects of morphine and that this differential sensitivity is evident early in development and is developmentally stable. The basis for these strain differences in morphine-induced avoidance was discussed.

  4. Enhanced morphine-induced antinociception in histamine H3 receptor gene knockout mice.

    PubMed

    Mobarakeh, Jalal Izadi; Takahashi, Kazuhiro; Yanai, Kazuhiko

    2009-09-01

    Previous studies have implicated a potential role for histamine H3 receptor in pain processing. There have been conflicting data, however, on the roles of H3 receptors in pain perception, and little information is available about the role of spinal histamine H3 receptors in morphine-induced antinociception. In the present study we examined the role of histamine H3 receptor in morphine-induced antinociception using histamine H3 receptor knockout mice and a histamine H3 receptor antagonist. Anitinociception was evaluated by assays for four nociceptive stimuli: hot-plate, tail-flick, paw-withdrawal, and formalin tests. Antinociception induced by morphine (0.125 nmol/5 microl, i.t.) was significantly augmented in histamine H3 receptor knockout (-/-) mice compared to the wild-type (+/+) mice in all four assays of pain. Furthermore, the effect of intrathecally administered morphine with thioperamide, a histamine H3 antagonist, was examined in C57BL/6J mice. A low dose of i.t. administered thioperamide (0.125 nmol/5 microl) alone had no significant effect on the nociceptive response. In contrast, the combination of morphine (0.125 nmol/5 microl, i.t.) with the same dose of thioperamide resulted in a significant reduction in the pain-related behaviors in all four nociceptive tests. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H3 receptors at the spinal level.

  5. Morphine induces Beclin 1- and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus.

    PubMed

    Zhao, Lixia; Zhu, Yushan; Wang, Dongmei; Chen, Ming; Gao, Ping; Xiao, Weiming; Rao, Guanhua; Wang, Xiaohui; Jin, Haijing; Xu, Lin; Sui, Nan; Chen, Quan

    2010-04-01

    Chronic exposure to morphine can induce drug addiction and neural injury, but the exact mechanism is not fully understood. Here we show that morphine induces autophagy in neuroblastoma SH-SY5Y cells and in the rat hippocampus. Pharmacological approach shows that this effect appears to be mediated by PTX-sensitive G protein-coupled receptors signaling cascade. Morphine increases Beclin 1 expression and reduces the interaction between Beclin 1 and Bcl-2, thus releasing Beclin 1 for its pro-autophagic activity. Bcl-2 overexpression inhibits morphine-induced autophagy, whereas knockdown of Beclin 1 or knockout of ATG5 prevents morphine-induced autophagy. In addition, chronic treatment with morphine induces cell death, which is increased by autophagy inhibition through Beclin 1 RNAi. Our data are the first to reveal that Beclin 1 and ATG5 play key roles in morphine-induced autophagy, which may contribute to morphine-induced neuronal injury.

  6. Morphine-induced anxiolytic-like effect in morphine-sensitized mice: involvement of ventral hippocampal nicotinic acetylcholine receptors.

    PubMed

    Rezayof, Ameneh; Assadpour, Sara; Alijanpour, Sakineh

    2013-01-01

    In the present study, the effects of repeated intra-ventral hippocampal (intra-VH) microinjections of nicotinic acetylcholine receptor agonist or antagonist on morphine-induced anxiolytic-like behavior were investigated in morphine-sensitized mice using elevated plus-maze. Intraperitoneal (i.p.) administration of different doses of morphine (5, 7.5 and 10mg/kg) increased the percentage of open arm time (%OAT), open arm entries (%OAE), but not locomotor activity, indicating an anxiolytic-like response to morphine. The maximum response was obtained by 7.5mg/kg of the opioid. The anxiety-like behavior which was induced by a lower dose of morphine (5mg/kg) was significantly increased in mice that had previously received once daily injections of morphine (10 and 20mg/kg, i.p.) for 3 days. It should be considered that this treatment also increased locomotor activity in morphine-sensitized mice. Furthermore, the response to an ineffective dose of morphine (5mg/kg, i.p.) in the EPM was significantly increased in the animals that had previously received nicotine for 3 days (0.1, 0.3, 0.5 and 0.7 μg/mouse; intra-VH), 5 min prior to the injections of morphine (5mg/kg/day × 3 days; i.p.). On the other hand, the increase of morphine-induced anxiolytic-like effect in animals that had previously received the 3-day morphine (20mg/kg) was dose dependently suppressed by once daily injections of mecamylamine (0.5, 1 and 2 μg/mouse/day × 3 days; intra-VH). It is important to note that repeated intra-VH administrations of the same doses of nicotine or mecamylamine alone caused no significant change in morphine (5mg/kg)-induced anxiety-like parameters in the EPM. In conclusion, it seems that morphine sensitization affects the anxiety-like behavior in the EPM and the cholinergic system in the ventral hippocampus, via nicotinic receptors, may play an important role in this effect.

  7. Activation of phosphatidylinositol 3-kinase/Akt-mammalian target of Rapamycin signaling pathway in the hippocampus is essential for the acquisition of morphine-induced place preference in rats.

    PubMed

    Cui, Yue; Zhang, X Q; Cui, Y; Xin, W J; Jing, J; Liu, X G

    2010-11-24

    Hippocampus is a critical structure for the acquisition of morphine-induced conditioned place preference (CPP), which is a usual learning paradigm for assessing drug reward. However, the precise mechanisms remain largely unknown. Phosphatidylinositol 3-kinase (PI3K) and its downstream targets, including Akt, mammalian target of Rapamycin (mTOR) and 70-kDa ribosomal S6 kinase (p70S6K), are critical molecules implicated in learning and memory. Here, we tested the role of PI3K/Akt-mTOR-p70S6K signaling pathway in morphine-induced CPP in the hippocampus. Our results showed that the acquisition of morphine CPP increased phosphorylation of Akt in the hippocampal CA3, but not in the nucleus accumbens (NAc), the ventral tegmental area (VTA) or the CA1. Moreover, the phosphorylated Akt exclusively expressed in the CA3 neurons. Likewise, levels of phosphorylated mTOR and p70S6K were significantly enhanced in the CA3 following morphine CPP. The alterations of these phosphorylated proteins are positively correlated with the acquisition of morphine CPP. More importantly, microinjection of PI3K inhibitor (LY294002) or mTOR inhibitor (Rapamycin) into the CA3 prevented the acquisition of CPP and inhibited the activation of PI3K-Akt signaling pathway. In addition, pre-infusion of β-FNA (β-funaltrexamine hydrochloride), a selective irreversible μ opioid receptor antagonist, into CA3 significantly prevented the acquisition of CPP and impaired Akt phosphorylation. All these results strongly implied that the PI3K-Akt signaling pathway activated by μ opioid receptor in hippocampal CA3 plays an important role in acquisition of morphine-induced CPP.

  8. Comparison of mirtazapine, gabapentin and ondansetron to prevent intrathecal morphine-induced pruritus

    PubMed Central

    Akhan, Ayse; Subasi, Ferhunde Dilek; Bosna, Gulsen; Ekinci, Osman; Pamuk, Hakan; Batan, Siddika; Ateser, Rezzan Yagmur; Turan, Gulden

    2016-01-01

    OBJECTIVE: Antagonism of the central nervous system inhibitor neurotransmitter gamma-Aminobutyric acid (GABA) or serotonergic system activation is an important factor in the pathogenesis of intrathecal morphine-induced pruritus. This study tested the hypothesis that preoperative use of ondansetron, gabapentin or mirtazapine can prevent morphine-induced pruritus. METHODS: We randomly allocated 80 patients of American Society of Anesthesiology (ASA) classification I and II physical status who were to undergo unilateral inguinal hernia or pilonidal sinus operations under spinal anesthesia into 4 equal groups. The first 3 groups received oral doses of 30 mg mirtazapine, 8 mg ondansetron, and 1200 mg gabapentin at 2 hours, 10 minutes, and 1 hour before surgery, respectively, and the fourth group was given a placebo. All patients received intrathecal injection of 15 mg of 0.5% hyperbaric bupivacaine and 0.2 mg morphine. Pruritus was evaluated at 0, 3, 6, 9, 12, and 24 hours after intrathecal morphine administration, and details of presence, onset time, duration, localization, and severity of pruritus were recorded. RESULTS: Incidence of pruritus was significantly more frequent in the placebo group compared to ondansetron, gabapentin, and mirtazapine groups (70%, 55%, 35%, and 35%, respectively). In general, onset of pruritus was between 2 and 6 hours after intrathecal morphine injection; however, onset in the gabapentin group (mean±SD: 4.75±2.7 hours; p=0.019) was delayed compared to other groups. It was observed that pruritus persisted relatively longer in the ondansetron and placebo groups (mean±SD: 6±3.08; 5.82±2.96 hours, respectively; p=0.047). No statistical determination was made regarding location of pruritus. Severity of pruritus was greater in the placebo group (p=0.0001). Necessity for antipruritic treatment was not statistically significantly different between groups. CONCLUSION: Incidence and severity of intrathecal morphine-induced pruritus decreased

  9. Neuroprotection of donepezil against morphine-induced apoptosis is mediated through Toll-like receptors.

    PubMed

    Shafie, Alireza; Moradi, Farshid; Izadpanah, Esmael; Mokarizadeh, Aram; Moloudi, Mohammad Raman; Nikzaban, Mehrnoush; Hassanzadeh, Kambiz

    2015-10-05

    Previously, we had shown that donepezil provides anti-apoptotic effects associated with the prevention of morphine tolerance to the analgesic effect. In this regard, the present study aimed to evaluate the molecular mechanisms involved in this effect considering the possible role of Toll-like receptor (TLR) 2,4, and the balance between pre-apoptotic and anti-apoptotic Bcl family proteins. To this end, male Wistar rats received daily morphine in combination with either normal saline or donepezil (0.5, 1, or 1.5 mg/kg, ip). The analgesic effect was assessed by the plantar test apparatus. The latency was recorded when the animal responded to the light stimulus. On the 15th day, when no significant difference was observed between morphine and saline groups in terms of analgesia, the frontal cortex and lumbar spinal cord of the animals were dissected. Then, TLR2 and 4, Bcl2, and Bax mRNA fold changes were calculated using Real-time PCR method. The results indicated no significant analgesic effect in the morphine group compared with the saline treated animals after 15 days of injection, while daily co-administration of donepezil with morphine preserved significant analgesia. Moreover, Quantitative PCR showed that morphine significantly increased TLRs and Bax gene expressions and decreased the anti-apoptotic Bcl2. In contrast, donepezil prevented these morphine induced changes in the mentioned gene expressions. Taken together, the results suggest that the neuroprotective effects of donepezil in attenuating morphine-induced tolerance and apoptosis are mediated by preventing morphine-induced changes in TLR2 and 4 gene expressions.

  10. Morphine-induced Straub tail reaction in mice treated with serotonergic compounds.

    PubMed

    Belozertseva, Irina V; Dravolina, Olga A; Tur, Margarita A; Semina, Marina G; Zvartau, Edwin E; Bespalov, Anton Yu

    2016-11-15

    Constitutively active 5-HT2 receptors have been suggested to contribute to motoneuronal excitability, muscle spasms and spasticity. Accordingly, 5-HT2C receptor inverse agonists have been demonstrated in pilot experiments to reduce spasticity in animal model of spasticity and patients with spinal cord injuries. Thus, 5-HT2C receptor inverse agonists may represent a novel class of anti-spasticity agents justifying a search for compounds with robust 5-HT2C receptor inverse agonist activity either among the existing medications or via a dedicated drug discovery program. Morphine-induced Straub tail response in mice is regarded as a model of transient spasticity that may be suitable for supporting such drug discovery efforts. Subcutaneous injection of morphine (10-60mg/kg) induced a dose-dependent Straub tail reaction in male Swiss mice with maximum response obtained 15-30min after the morphine administration. When given prior to morphine, 5-HT2B/2C receptor inverse agonists cyproheptadine (1-10mg/kg, i.p.) and SB206553 (0.3-3mg/kg, i.p.) diminished Straub tail reaction dose-dependently without affecting spontaneous locomotor activity. In contrast, 5-HT2B/2C receptor antagonist methysergide (1-5.6mg/kg, i.p.) and 5-HT2C receptor antagonist SB242084 (1-5.6mg/kg, i.p.) as well as 5-HT2A receptor inverse agonist pimavanserin (1-10mg/kg, i.p.) had no appreciable effects on Straub tail response. Taken together, the findings indicate that constitutive activity of 5-HT2B/2C receptor may be involved in the mechanisms of morphine-induced spasticity. Thus, morphine-induced Straub tail response may be evaluated further as a candidate higher throughput test to identify 5-HT2C receptor inverse agonists with anti-spasticity effects in vivo.

  11. 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

  12. Effect of Aqueous Extract of Crocus sativus L. on Morphine-Induced Memory Impairment

    PubMed Central

    Naghibi, Sayede Maryam; Hosseini, Mahmoud; Khani, Fatemeh; Rahimi, Motahare; Vafaee, Farzaneh; Rakhshandeh, Hassan; Aghaie, Azita

    2012-01-01

    In the present study, the effect of aqueous extracts of saffron on morphine-induced memory impairment was investigated. On the training trial, the mice received an electric shock when the animals were entered into the dark compartment. Twenty-four and forty-eight hours later, the time latency for entering the dark compartment was recorded and defined as the retention trial. The mice were divided into (1) control, (2) morphine which received morphine before the training in the passive avoidance test, (3–5) three groups treated by 50, 150 and 450 mg/kg of saffron extract before the training trial, and (6 and 7) the two other groups received 150 and 450 mg/kg of saffron extract before the retention trial. The time latency in morphine-treated group was lower than control (P < 0.01). Treatment of the animals by 150 and 450 mg/kg of saffron extract before the training trial increased the time latency at 24 and 48 hours after the training trial (P < 0.05 and P < 0.01). Administration of both 150 and 450 mg/kg doses of the extract before retention trials also increased the time latency (P < 0.01). The results revealed that the saffron extract attenuated morphine-induced memory impairment. PMID:23091484

  13. Effect of Aqueous Extract of Crocus sativus L. on Morphine-Induced Memory Impairment.

    PubMed

    Naghibi, Sayede Maryam; Hosseini, Mahmoud; Khani, Fatemeh; Rahimi, Motahare; Vafaee, Farzaneh; Rakhshandeh, Hassan; Aghaie, Azita

    2012-01-01

    In the present study, the effect of aqueous extracts of saffron on morphine-induced memory impairment was investigated. On the training trial, the mice received an electric shock when the animals were entered into the dark compartment. Twenty-four and forty-eight hours later, the time latency for entering the dark compartment was recorded and defined as the retention trial. The mice were divided into (1) control, (2) morphine which received morphine before the training in the passive avoidance test, (3-5) three groups treated by 50, 150 and 450 mg/kg of saffron extract before the training trial, and (6 and 7) the two other groups received 150 and 450 mg/kg of saffron extract before the retention trial. The time latency in morphine-treated group was lower than control (P < 0.01). Treatment of the animals by 150 and 450 mg/kg of saffron extract before the training trial increased the time latency at 24 and 48 hours after the training trial (P < 0.05 and P < 0.01). Administration of both 150 and 450 mg/kg doses of the extract before retention trials also increased the time latency (P < 0.01). The results revealed that the saffron extract attenuated morphine-induced memory impairment.

  14. Possible involvement of nitric oxide in morphine-induced miosis and reduction of intraocular pressure in rabbits.

    PubMed

    Bonfiglio, Vincenza; Bucolo, Claudio; Camillieri, Giovanni; Drago, Filippo

    2006-03-18

    The role of mu3 opioid receptors in morphine-induced intraocular pressure (IOP) lowering effect and miosis was evaluated in conscious, dark-adapted New Zealand white (NZW) rabbits using a masked-design study. IOP and pupil diameter (PD) measurements were taken at just before and 0.5, 1, 2, 4, 6 h after monolateral instillation of morphine (10, 50 and 100 microg/30 microl) as compared to vehicle administered in the contralateral eye. Morphine-induced ocular effects were challenged by a pre-treatment with the non-selective opioid receptor antagonist, naloxone (100 microg/30 microl), the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 1%, 30 microl), or the non-selective mu3 opioid receptor inhibitor, reduced L-glutathione (GSH, 1%, 30 microl). Morphine induced a dose-dependent decrease in IOP and PD. Pre-treatment with naloxone totally prevented morphine-induced decrease in IOP and miosis. Ocular administration of L-NAME or GSH alone failed to affect IOP or PD of NZW rabbits. However, pre-treatment with either drugs significantly reduced, but not totally prevented ocular effects of morphine. These results suggest that biochemical mechanisms related to nitric oxide release are involved, at least in part, in morphine effects on the eye. Since the mu3 opioid receptor subtype is able to release nitric oxide and is sensitive to inactivation by GSH, it may be possible that mu3 opioid receptors are involved in morphine-induced miosis and reduction in IOP.

  15. Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance.

    PubMed

    Contreras, E; Tamayo, L; Amigo, M

    1988-04-13

    The influence of calcium channel blockers on morphine-induced analgesia and on tolerance to the chronic administration of the opiate was investigated in mice. The effects of a test dose of morphine were significantly increased by the administration of diltiazem, flunarizine, nicardipine and verapamil. In contrast, nifedipine induced an antagonistic effect. The calcium channel antagonists did not change the reaction time to thermal stimulation in mice (hot plate test). The administration of nifedipine, flunarizine and verapamil reduced the intensity of the tolerance induced by a single dose of morphine administered in a slow release preparation. Diltiazem induced a non-significant decrease of the process. The present results are in accordance with the known interaction of acute and chronic morphine administration with the intracellular calcium concentration in neurones of the central nervous system.

  16. 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

  17. Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats.

    PubMed

    Wen, Di; Zang, Guoqing; Sun, DongLei; Yu, Feng; Mei, Dong; Ma, Chunling; Cong, Bin

    2014-01-24

    Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1μg, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1μg, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10μg, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10μg, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.

  18. Neuromodulatory effects of the dorsal hippocampal endocannabinoid system in dextromethorphan/morphine-induced amnesia.

    PubMed

    Ghasemzadeh, Zahra; Rezayof, Ameneh

    2017-01-05

    Dextromethorphan which is an active ingredient in many cough medicines has been previously shown to potentiate amnesic effect of morphine in rats. However, the effect of dextromethorphan, that is also a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in combination with morphine on hippocampus-based long term memory has not been well characterized. The aim of the present study was to assess the possible role of endocannabinoid system of the dorsal hippocampus in dextromethorphan /morphine-induced amnesia. Our results showed that intraperitoneal (i.p.) injection of morphine (5mg/kg) or dextromethorphan (5-15mg/kg) before testing the passive avoidance learning induced amnesia. Combination of ineffective doses of dextromethorphan (7.5mg/kg, i.p.) and morphine (2mg/kg, i.p.) also produced amnesia, suggesting the enhancing effects of the drugs. To assess the effect of the activation or inhibition of the dorsal hippocampal cannabinoid CB1 receptors on this amnesia, ACPA or AM251 as selective receptor agonists or antagonists were respectively injected into the CA1 regions before systemic injection of dextromethorphan and morphine. Interestingly, intra-CA1 microinjection of ACPA (0.5-1ng/rat) improved the amnesic effect of dextromethorphan /morphine combination. The microinjection of AM251 into the CA1 region enhanced the response of the combination of dextromethorphan /morphine in inducing amnesia. Moreover, Intra-CA1 microinjection of AM251 inhibited the improving effect of ACPA on dextromethorphan /morphine-induced amnesia. It is important to note that intra-CA1 microinjection of the same doses of the agonist or antagonist by itself had no effects on memory formation. Thus, it can be concluded that the dorsal hippocampal endocannabinoid system, via CB1 receptor-dependent mechanism, may be involved in morphine/dextromethorphan -induced amnesia.

  19. 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

  20. COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia

    PubMed Central

    Farooqui, M; Li, Y; Rogers, T; Poonawala, T; Griffin, R J; Song, C W; Gupta, K

    2007-01-01

    Morphine and its congener opioids are the main therapy for severe pain in cancer. However, chronic morphine treatment stimulates angiogenesis and tumour growth in mice. We examined if celecoxib (a cyclooxygenase-2 (COX-2) inhibitor) prevents morphine-induced tumour growth without compromising analgesia. The effect of chronic treatment with celecoxib (by gavage) and/or morphine (subcutaneously), or PBS on tumour prostaglandin E2 (PGE2), COX-2, angiogenesis, tumour growth, metastasis, pain behaviour and survival was determined in a highly invasive SCK breast cancer model in A/J mice. Two weeks of chronic morphine treatment at clinically relevant doses stimulates COX-2 and PGE2 (4.5-fold compared to vehicle alone) and angiogenesis in breast tumours in mice. This is accompanied by increased tumour weight (∼35%) and increased metastasis and reduced survival. Co-administration of celecoxib prevents these morphine-induced effects. In addition, morphine and celecoxib together provided better analgesia than either agent alone. Celecoxib prevents morphine-induced stimulation of COX-2, PGE2, angiogenesis, tumour growth, metastasis and mortality without compromising analgesia in a murine breast cancer model. In fact, the combination provided significantly better analgesia than with morphine or celecoxib alone. Clinical trials of this combination for analgesia in chronic and severe pain in cancer are warranted. PMID:17971769

  1. 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.

  2. Biomarkers of morphine tolerance and dependence are prevented by morphine-induced endocytosis of a mutant μ-opioid receptor

    PubMed Central

    He, Li; Kim, Joseph A.; Whistler, Jennifer L.

    2009-01-01

    Growing evidence shows that trafficking of the μ-opioid receptor (MOR) is a critical process in functional recovery from desensitization following activation and plays important roles in morphine tolerance and dependence largely because of the failure of morphine to promote such trafficking. However, morphine tolerance and dependence are believed to be mediated by multiple mechanisms, including well-documented biochemical changes in cAMP activity, N-methyl-d-aspartate receptors (NMDARs), glucocorticoid receptors (GRs), and c-fos. Here, we assess the consequences of promoting morphine-induced endocytosis on these biochemical changes utilizing a knock-in mouse model, RMOR, in which MORs undergo morphine-induced endocytosis. Chronic morphine treatment of wild-type (WT) mice promoted superactivation of adenylyl cyclase, alterations in NMDARs, and up-regulation of GR and c-fos in distinct brain regions. Notably, none of these biochemical changes occurred in the RMOR-knock-in mice. Together, these data demonstrate that morphine tolerance and dependence are mediated by multiple biochemical mechanisms and that MOR endocytosis plays a critical role in each of these mechanisms.—He, L., Kim, J. A., Whistler, J. L. Biomarkers of morphine tolerance and dependence are prevented by morphine-induced endocytosis of a mutant μ-opioid receptor. PMID:19679639

  3. Cannabinoid CB2 receptor attenuates morphine-induced inflammatory responses in activated microglial cells

    PubMed Central

    Merighi, Stefania; Gessi, Stefania; Varani, Katia; Fazzi, Debora; Mirandola, Prisco; Borea, Pier Andrea

    2012-01-01

    BACKGROUND AND PURPOSE Among several pharmacological properties, analgesia is the most common feature shared by either opioid or cannabinoid systems. Cannabinoids and opioids are distinct drug classes that have been historically used separately or in combination to treat different pain states. In the present study, we characterized the signal transduction pathways mediated by cannabinoid CB2 and µ-opioid receptors in quiescent and LPS-stimulated murine microglial cells. EXPERIMENTAL APPROACH We examined the effects of µ-opioid and CB2 receptor stimulation on phosphorylation of MAPKs and Akt and on IL-1β, TNF-α, IL-6 and NO production in primary mouse microglial cells. KEY RESULTS Morphine enhanced release of the proinflammatory cytokines, IL-1β, TNF-α, IL-6, and of NO via µ-opioid receptor in activated microglial cells. In contrast, CB2 receptor stimulation attenuated morphine-induced microglial proinflammatory mediator increases, interfering with morphine action by acting on the Akt-ERK1/2 signalling pathway. CONCLUSIONS AND IMPLICATIONS Because glial activation opposes opioid analgesia and enhances opioid tolerance and dependence, we suggest that CB2 receptors, by inhibiting microglial activity, may be potential targets to increase clinical efficacy of opioids. PMID:22428664

  4. Differences in morphine-induced antinociception in male and female offspring born of morphine exposed mothers

    PubMed Central

    Biglarnia, Masoomeh; Karami, Manizheh; Hafshejani, Zahra Khodabakhshi

    2013-01-01

    Objective: Antinociceptive effect of morphine in offspring born of mothers that received saline or morphine during the gestation period was investigated. Materials and Methods: Wistar rats (200-250 g) received saline, morphine 0.5 mg/kg or 5 mg/kg during gestation days 14-16. All pups after weaning were isolated treatment/sex dependently and were allowed to fully mature. The antinociceptive effect of morphine was assessed in formalin test. Morphine (0.5-7.5 mg/kg) or saline (1 ml/kg) was injected intraperitoneally 10 min before formalin (50 μl of 2.5% solution in right hind-paw). Results: Male offspring born of saline-treated mothers were less morphine-sensitive than females. On the contrary, male offspring exposed prenatally to morphine (5 mg/kg) were more sensitive to morphine-induced antinociceptive response in formalin test. However, no difference in antinociceptive effect was observed amongst offspring of either sex born of mothers treated with morphine 0.5 mg/kg, identifying a lower dose effect of the opioid. Conclusion: The exposure to morphine during the developmental period may result in altered development of tolerance to morphine and thus involved in drug abuse. PMID:23833363

  5. Behavioral cross-sensitization between morphine-induced locomotion and sodium depletion-induced salt appetite.

    PubMed

    Na, Elisa S; Morris, Michael J; Johnson, Alan Kim

    2009-10-01

    In general terms, sensitization refers to the capacity of a repetitive stimulus of fixed strength to produce a progressive increase in the magnitude of a response with each stimulation. In the addiction literature cross-sensitization is the capacity of an agent with abuse potential to sensitize a behavioral response induced by another stimulus. In the present experiments we examined the effects of morphine pretreatment on furosemide-induced saline intake and conversely sodium appetite induction on morphine-induced locomotion. In an initial experiment rats were pretreated with morphine (10 mg/kg, s.c.) or vehicle for 5 days. The rats were then sodium or sham depleted and 24 h later given a sodium appetite test. Sodium depleted rats pretreated with morphine increased saline intake compared to depleted rats initially pretreated with vehicle. In a second experiment rats that were previously depleted and repleted of sodium as compared to sham depleted animals showed enhanced locomotor activity in an open field test when challenged with morphine (1 mg/kg, s.c.). These studies demonstrate that the behavioral responses induced by sodium deficiency and morphine treatment cross-sensitize with one another and suggest that common neural substrates underlie the sensitization of behaviors associated with states induced by morphine and sodium appetite.

  6. 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.

  7. 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

    2016-09-06

    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.

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

    PubMed

    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.

  9. Involvement of GABA(B) receptors of the dorsal hippocampus on the acquisition and expression of morphine-induced place preference in rats.

    PubMed

    Zarrindast, Mohammad-Reza; Massoudi, Roohollah; Sepehri, Houri; Rezayof, Ameneh

    2006-01-30

    In the present study, effects of intra-hippocampal CA1 (intra-CA1) injections of GABA(B) receptor agonist and antagonist on the acquisition and expression of morphine-induced place preference in male Wistar rats have been investigated. Subcutaneous administration of different doses of morphine sulphate (0.5-6 mg/kg) produced a dose-dependent conditioned place preference (CPP). Using a 3-day schedule of conditioning, it was found that the GABA(B) receptor agonist, baclofen (0.5-2 microg/rat; intra-CA1), or the GABA(B) receptor antagonist, phaclofen (1-3 microg/rat; intra-CA1), did not produce a significant place preference or place aversion. Intra-CA1 administration of baclofen (1 and 2 microg/rat; intra-CA1) decreased the acquisition of CPP induced by morphine (3 mg/kg; s.c.). On the other hand, intra-CA1 injection of phaclofen (1 and 2 microg/rat; intra-CA1) in combination with a lower dose of morphine (1 mg/kg) elicited a significant CPP. The response of baclofen (2 microg/rat; intra-CA1) was reversed by phaclofen (4 and 6 microg/rat; intra-CA1). Furthermore, intra-CA1 administration of baclofen but not phaclofen before testing significantly decreased the expression of morphine (3 mg/kg; s.c.)-induced place preference. Baclofen or phaclofen injections had no effects on locomotor activity on the testing sessions. It is concluded that the GABA(B) receptors in dorsal hippocampus may play an active role in morphine reward.

  10. The antipsychotic aripiprazole selectively prevents the stimulant and rewarding effects of morphine in mice.

    PubMed

    Almeida-Santos, Ana F; Gobira, Pedro H; Souza, Diego P; Ferreira, Renata C M; Romero, Thiago R; Duarte, Igor D; Aguiar, Daniele C; Moreira, Fabricio A

    2014-11-05

    Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors, with a favorable pharmacological profile. Due to its unique mechanism of action, this compound has potential application as a substitutive therapy for drug addiction. Considering that distinct neural systems subserve the addictive and analgesic actions of opioids, we tested the hypothesis that aripiprazole selectively inhibit the abuse-related, but not the antinociceptive, effects of morphine. The drugs were tested in male Swiss mice for their effects on locomotion, conditioned place preference (CPP) and nociception. Morphine (20mg/kg) increased motor activity, whereas aripiprazole (0.1, 1 and 10mg/kg) did not induce any change. This antipsychotic, however, prevented morphine-induced locomotion. In the conditioning box, aripiprazole did not induce either reward or aversion. Yet, it prevented both the acquisition and the expression of morphine-induced CPP. Finally, none of the doses of this antipsychotic interfere with morphine (5mg/kg)-induced antinociception in the tail-flick test. In conclusion, aripiprazole inhibited the abuse-related effects of morphine at doses that do not interfere with basal locomotion, reward or aversion. Also, it did not alter morphine-induced antinociceptive effects. This antipsychotic should be further investigated as a possible substitutive strategy for treating certain aspects of opioid addiction.

  11. Altered Morphine-Induced Analgesia in Neurotensin Type 1 Receptor Null Mice

    PubMed Central

    Roussy, Geneviève; Beaudry, Hélène; Lafrance, Mylène; Belleville, Karine; Beaudet, Nicolas; Wada, Keiji; Gendron, Louis; Sarret, Philippe

    2013-01-01

    Both neurotensin (NT) and opioid agonists have been shown to induce antinociception in rodents after central administration. Besides, previous studies have revealed the existence of functional interactions between NT and opioid systems in the regulation of pain processing. We recently demonstrated that NTS1 receptors play a key role in the mediation of the analgesic effects of NT in long-lasting pain. In the present study, we therefore investigated whether NTS1 gene deletion affected the antinociceptive action of mu opioid drugs. To this end, pain behavioral responses to formalin were determined following systemic administration of morphine in both male and female NTS1 knockout mice. Acute injection of morphine (2 or 5 mg/kg) produced strong antinociceptive effects in both male and female wild-type littermates, with no significant sex differences. On the other hand, morphine analgesia was considerably reduced in NTS1-deficient mice of both sexes compared to their respective controls, indicating that the NTS1 receptor actively participates in mu opioid alleviating pain. By examining specifically the flinching, licking and biting nociceptive behaviors, we also showed that the functional crosstalk between NTS1 and mu opioid receptors influences the supraspinally-mediated behaviors. Interestingly, sexual dimorphic action of morphine-induced pain inhibition was found in NTS1 null mice in the formalin test, suggesting that the endogenous NT system interacts differently with the opioid network in male and female mice. Altogether, these results demonstrated that NTS1 receptor activation operates downstream to the opioidergic transmission and that NTS1-selective agonists combined with morphine may act synergistically to reduce persistent pain. PMID:20727387

  12. Effects of cholecystokinin-8 on morphine-induced spatial reference memory impairment in mice.

    PubMed

    Yang, Shengchang; Wen, Di; Dong, Mei; Li, Dong; Sun, Donglei; Ma, Chunling; Cong, Bin

    2013-11-01

    Acute and chronic exposure to opiate drugs impaired various types of memory processes. To date, there is no preventive treatment for opiate-induced memory impairment and the related mechanism is still unclear. CCK-8 is the most potent endogenous anti-opioid peptide and has been shown to exert memory-enhancing effect, but the effect of CCK-8 on morphine-induced memory impairment has not been reported. By using Morris water maze, we found that escape latency to the hidden platform in navigation test was not influenced, but performance in the probe test was seriously poor in morphine dependency mice. Amnesia induced by chronic morphine treatment was significantly alleviated by pre-treatment with CCK-8 (0.01, 0.1 and 1 μg, i.c.v.), and CCK-8 (0.1 and 1 μg, i.c.v.) treatment alone could improve performance in either navigation or probe test. Furthermore, Golgi-Cox staining analysis revealed that pre-treatment with CCK-8 (1 μg, i.c.v.) reversed spine density decreased in CA1 region of hippocampus in morphine dependency mice, and CCK-8 (1 μg, i.c.v.) alone obviously increased spine density in CA1. Our findings conclude spine density change in CA1 region of hippocampus may be the structural plasticity mechanism which is responsible for enhancing effect of CCK-8 on spatial reference memory. Therefore, CCK-8 could effectively improve memory impairment in morphine dependency mice.

  13. Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat.

    PubMed

    Fadda, Paola; Scherma, Maria; Fresu, Alessandra; Collu, Maria; Fratta, Walter

    2003-10-01

    Evidence recently provided has suggested a specific involvement of the GABAergic system in modulating positive reinforcing properties of several drugs of abuse through an action on mesolimbic dopaminergic neurons. The GABA(B) receptor agonist baclofen has been proposed as a potential therapeutic agent for the clinical treatment of several forms of drug addiction. In the present study, using the in vivo microdialysis technique, we investigated the effect of baclofen on nicotine, cocaine, and morphine-induced increase in extracellular dopamine (DA) levels in the shell of the nucleus accumbens, a brain area supposedly involved in the modulation of the central effects of several drugs of abuse, of freely moving rats. As expected, nicotine (0.6 mg/kg s.c.), morphine (5 mg/kg s.c.), and cocaine (7.5 mg/kg i.p.) administration in rats induced a marked increase in extracellular DA concentrations in the nucleus accumbens, reaching a maximum value of +205 +/- 8.4%, +300 +/- 22.2%, and +370 +/- 30.7%, respectively. Pretreatment with baclofen (1.25 and 2.5 mg/kg i.p.) dose-dependently reduced the nicotine-, morphine-, and cocaine-evoked DA release in the shell of the nucleus accumbens. Furthermore, baclofen alone did not elicit changes in basal DA extracellular levels up to 180 min. Taken together, our data are in line with previous reports demonstrating the ability of baclofen to modulate the mesolimbic DAergic transmission and indicate baclofen as a putative candidate in the pharmacotherapy of polydrug abuse.

  14. Role of fosaprepitant, a neurokinin Type 1 receptor antagonist, in morphine-induced antinociception in rats

    PubMed Central

    Prasoon, Pranav; Gupta, Shivani; Kumar, Rahul; Gautam, Mayank; Kaler, Saroj; Ray, Subrata Basu

    2016-01-01

    Objectives: Opioids such as morphine form the cornerstone in the treatment of moderate to severe pain. However, opioids also produce serious side effects such as tolerance. Fosaprepitant is a substance P (SP) receptor antagonist, which is used for treating chemotherapy-induced nausea and vomiting. SP is an important neuropeptide mediating transmission of pain at the spinal level. Thus, it was hypothesized that combining morphine with fosaprepitant would increase the antinociceptive effect of morphine. The objectives were to evaluate the effect of fosaprepitant on morphine-induced antinociception in rats and to investigate its mechanism of action. Methods: Sprague-Dawley rats were injected with morphine (10 mg/kg twice daily) and/or fosaprepitant (30 mg/kg once daily) for 7 days. Pain threshold was assessed by the hot plate test. Expression of SP and calcitonin gene-related peptide (CGRP) in the spinal cords of these rats was evaluated by immunohistochemistry. Results: Morphine administration resulted in an antinociceptive effect compared to the control group (day 1 and to a lesser extent on day 4). The decreased antinociception despite continued morphine treatment indicated development of tolerance. Co-administration of fosaprepitant attenuated tolerance to morphine (days 1 and 3) and increased the antinociceptive effect compared to control group (days 1–4). Expression of SP was increased in the morphine + fosaprepitant group. Conclusions: The results show that fosaprepitant attenuates the development of tolerance to morphine and thereby, increases the antinociceptive effect. This is likely linked to decreased release of SP from presynaptic terminals. PMID:27756950

  15. Morphine-induced conditioned place preference and the alterations of p-ERK, p-CREB and c-fos levels in hypothalamus and hippocampus: the effects of physical stress.

    PubMed

    Pahlevani, P; Fatahi, Z; Moradi, M; Haghparast, A

    2014-12-08

    The hypothalamus and hippocampus are important areas involved in stress responses and reward processing. In addition, ERK/CREB pathway plays a critical role in the control of cellular responses to stress and reward. In the current study, effects of acute and subchronic stress on the alteration of p-ERK, p-CREB and c-fos levels in the hypothalamus and hippocampus of saline- or morphine-treated animals during morphine-induced conditioned place preference (CPP) procedure were investigated. Male Wistar rats were divided into two saline- and morphine-treated supergroups. Each supergroup includes of control, acute stress and subchronic stress groups. In all of groups, the CPP procedure was done, afterward the alternation of p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level in the hypothalamus and hippocampus were estimated by Western blot analysis. The results indicated that in saline- or morphine-treated animals, p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level increased after application of acute and subchronic stress (except for p-ERK/ERK ratio in morphine-control group). Our findings revealed that in saline- or morphine-treated animals, acute and subcronic stress increased the p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level in the hypothalamus and hippocampus and this enhancement in morphine-treated animals, was more considerable than that in saline-treated animals.

  16. Effects of acute and long-term typical or atypical neuroleptics on morphine-induced behavioural effects in mice.

    PubMed

    Hollais, André W; Patti, Camilla L; Zanin, Karina A; Fukushiro, Daniela F; Berro, Laís F; Carvalho, Rita C; Kameda, Sonia R; Frussa-Filho, Roberto

    2014-03-01

    1. It has been suggested that the high prevalence of drug abuse in schizophrenics is related to chronic treatment with typical neuroleptics and dopaminergic supersensitivity that develops as a consequence. Within this context, atypical neuroleptics do not seem to induce this phenomenon. In the present study, we investigated the effects of acute administration or withdrawal from long-term administration of haloperidol and/or ziprasidone on morphine-induced open-field behaviour in mice. 2. In the first experiment, mice were given a single injection of haloperidol (1 mg/kg, i.p.) or several doses of ziprasidone (2, 4 or 6 mg/kg, i.p.) and motor activity was quantified by the open-field test. The aim of the second experiment was to verify the effects of an acute injection of haloperidol (1 mg/kg) or ziprasidone (6 mg/kg) on 20 mg/kg morphine-induced behaviours in the open-field test. In the third experiment, mice were treated with 1 mg/kg haloperidol and/or 2, 4 or 6 mg/kg ziprasidone for 20 days. Seventy-two hours after the last injection, mice were injected with 20 mg/kg, i.p., morphine and then subjected to the open-field test. Acute haloperidol or ziprasidone decreased spontaneous general activity and abolished morphine-induced locomotor stimulation. 3. Withdrawal from haloperidol or ziprasidone did not modify morphine-elicited behaviours in the open-field test. The results suggest that withdrawal from neuroleptic treatments does not contribute to the acute effect of morphine in schizophrenic patients.

  17. Potentiation of morphine-induced mechanical antinociception by σ₁ receptor inhibition: role of peripheral σ₁ receptors.

    PubMed

    Sánchez-Fernández, Cristina; Nieto, Francisco Rafael; González-Cano, Rafael; Artacho-Cordón, Antonia; Romero, Lucía; Montilla-García, Ángeles; Zamanillo, Daniel; Baeyens, José Manuel; Entrena, José Manuel; Cobos, Enrique José

    2013-07-01

    We studied the modulation of morphine-induced mechanical antinociception and side effects by σ₁ receptor inhibition. Both wild-type (WT) and σ₁ receptor knockout (σ₁-KO) mice showed similar responses to paw pressure (100-600 g). The systemic (subcutaneous) or local (intraplantar) administration of σ₁ antagonists (BD-1063, BD-1047, NE-100 and S1RA) was devoid of antinociceptive effects in WT mice. However, σ₁-KO mice exhibited an enhanced mechanical antinociception in response to systemic morphine (1-16 mg/kg). Similarly, systemic treatment of WT mice with σ₁ antagonists markedly potentiated morphine-induced antinociception, and its effects were reversed by the selective σ₁ agonist PRE-084. Although the local administration of morphine (50-200 μg) was devoid of antinociceptive effects in WT mice, it induced dose-dependent antinociception in σ₁-KO mice. This effect was limited to the injected paw. Enhancement of peripheral morphine antinociception was replicated in WT mice locally co-administered with σ₁ antagonists and the opioid. None of the σ₁ antagonists tested enhanced morphine-antinociception in σ₁-KO mice, confirming a σ₁-mediated action. Morphine-induced side-effects (hyperlocomotion and inhibition of gastrointestinal transit) were unaltered in σ₁-KO mice. These results cannot be explained by a direct interaction of σ₁ ligands with μ-opioid receptors or adaptive changes of μ-receptors in σ₁-KO mice, given that [(3)H]DAMGO binding in forebrain, spinal cord, and hind-paw skin membranes was unaltered in mutant mice, and none of the σ₁ drugs tested bound to μ-opioid receptors. These results show that σ₁ receptor inhibition potentiates morphine-induced mechanical analgesia but not its acute side effects, and that this enhanced analgesia can be induced at peripheral level.

  18. RACK1 affects morphine reward via BDNF.

    PubMed

    Wan, Lihong; Xie, Yizhou; Su, Lan; Liu, Yanyou; Wang, Yuhui; Wang, Zhengrong

    2011-10-06

    Chronic morphine addiction may trigger functional changes in the mesolimbic dopamine system, which is believed to be the neurobiological substrate of opiate addiction. Brain derived neurotrophic factor (BDNF) has been implicated in addiction-related pathology in animal studies. Our previous studies have shown that RACK1 is involved in morphine reward in mice. The recent research indicates nuclear RACK1 by localizing at the promoter IV region of the BDNF gene and the subsequent chromatin modifications leads to the activation of the promoter and transcription of BDNF. The present study was designed to investigate if shRACK1 (a short hairpin RNA of RACK1) could reverse the mice's behavioral responses to morphine and BDNF expression in hippocampus and prefrontal cortex. No significant changes were observed in vehicle-infused mice which received no morphine treatment (CONC) and shRACK1-infused mice which received no morphine treatment (CONR), whereas vehicle-infused mice preceded the morphine injection (MIC) showed increased BDNF expression in hippocampus and prefrontal cortex, as compared to vehicle-infused mice which received no morphine treatment (CONC). Intracerebroventricular shRACK1 treatment reversed these, and in fact, ShRACK1-infused mice preceded the morphine injection (MIR) showed reduced BDNF expression in hippocampus and prefrontal cortex, as compared to MIC. In the conditioned place preference (CPP) test, inactivating RACK1 markedly reduces morphine-induced conditioned place preference. Non-specific changes in CPP could not account for these effects since general CPP of shRACK1- and vehicle-infused animals was not different. Combined behavioral and molecular approaches have support the possibility that the RACK1-BDNF system plays an important role in the response to morphine-induced reward.

  19. Effects of an intrathecally administered benzodiazepine receptor agonist, antagonist and inverse agonist on morphine-induced inhibition of a spinal nociceptive reflex.

    PubMed Central

    Moreau, J. L.; Pieri, L.

    1988-01-01

    1. The effects of an intrathecally administered benzodiazepine receptor (BZR) agonist (midazolam, up to 50 micrograms), antagonist (flumazenil, Ro 15-1788, 5 micrograms) and inverse agonist (Ro 19-4603, 15 micrograms) on nociception and on morphine-induced antinociception were studied in rats. 2. By themselves, none of these compounds significantly altered pain threshold. 3. The BZR agonist midazolam enhanced the morphine-induced antinociceptive effect whereas the antagonist flumazenil did not alter it. In contrast, the BZR inverse agonist Ro 19-4603 decreased the morphine-induced antinociceptive effect. 4. Naloxone (1 mg kg-1 i.p.) completely reversed all these effects. 5. These results demonstrate that BZR agonists and inverse agonists are able to affect, by allosteric up- or down-modulation of gamma-aminobutyric acidA (GABAA)-receptors, the transmission of nociceptive information at the spinal cord level, when this transmission is depressed by mu-opioid receptor activation. PMID:2898960

  20. Morphine-induced sensitization of locomotor activity in mice: effect of social isolation on plasma corticosterone levels.

    PubMed

    Francès, H; Graulet, A; Debray, M; Coudereau, J P; Guéris, J; Bourre, J M

    2000-03-31

    This study examined the influence of social isolation on behavioural sensitization to the locomotor effect of morphine and the link between this behaviour and plasma corticosterone concentrations. Four weeks isolation induced an increase in the locomotor effect of morphine. In social and isolated mice, repeated administrations (6) of morphine (one injection every 3 or 4 days) followed by 3 h in an actimeter induced behavioural sensitization to the locomotor effect of morphine. No interaction was observed between social isolation and behavioural sensitization to morphine. Resocializing previously isolated mice for 3 weeks reduced the morphine-induced locomotor effect without altering the behavioural sensitization. Corticosterone plasma levels were more increased (416%) in mice isolated 5 weeks than in mice isolated for 2 weeks (243%) and they return to the control levels following 3 weeks of resocialization. Since there was no interaction between the increase in morphine locomotor effect induced by social isolation and the morphine-induced behavioural sensitization, it is suggested that each of these two events acts independently. Whether or not a common mechanism (plasma corticosterone levels?) partly underlies both effects, the result resembles a simple additive effect.

  1. 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

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

    PubMed

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

    2016-02-19

    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.

  3. Interactive HIV-1 Tat and morphine-induced synaptodendritic injury is triggered through focal disruptions in Na⁺ influx, mitochondrial instability, and Ca²⁺ overload.

    PubMed

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

    2014-09-17

    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 ([Ca(2+)]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 [Ca(2+)]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 [Ca(2+)]i were attenuated by the ryanodine receptor inhibitor ryanodine, as well as pyruvate. In summary, Tat induced increases in [Na(+)]i, mitochondrial instability, excessive Ca(2+) 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 [Ca(2+)]i and by further disrupting [Ca(2+)]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.

  4. 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

  5. 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.

  6. Intracerebroventricular effects of histaminergic agents on morphine-induced anxiolysis in the elevated plus-maze in rats.

    PubMed

    Zarrindast, Mohammad-Reza; Rostami, Parvin; Zarei, Morteza; Roohbakhsh, Ali

    2005-11-01

    Some reports indicate that morphine can induce anxiolytic effects both in animal and in man. It has also been reported that histaminergic system can interfere with some pharmacological effects of morphine. The effects of histaminergic agents on morphine-induced anxiolysis in rats, using elevated plus-maze were investigated in the present study. Intraperitoneal injection of morphine (3, 6 and 9 mg/kg) induced antianxiety effects. Intracerebroventricular administration of histamine at the doses of (5, 10 and 20 microg/rat) also increased anxiety-related behaviours. Intracerebroventricular injection of pyrilamine, a H1 receptor antagonist (25, 50 and 100 microg/rat), increased anxiety whereas injection of ranitidine, a H2 receptor antagonist (5, 10 and 20 microg/rat) at the same site, decreased anxiety. Therefore, it seems that histamine induces anxiogenic response through activation of H2 receptors, while the response of H1 blocker may be due to release of histamine. We also evaluated the interactions between morphine and histaminergic agents. Our data show that histamine (10 microg/rat), pyrilamine (50 microg/rat) and ranitidine (5 microg/rat) did not alter the response induced by different doses of morphine (3, 6 and 9 mg/kg). Similarly, a single dose of morphine did not alter the response induced by different doses of histamine (5, 10 and 20 microg/rat), pyrilamine (25, 50 and 100 microg/rat) or ranitidine (5, 10 and 20 microg/rat). In conclusion, the histaminergic system plays an important role in the modulation of anxiety, although in our experiments, no interaction was found between the effects of histaminergic agents and morphine on anxiety-related indices in the elevated plus-maze. This may imply that morphine-induced anxiolysis probably is independent of the histaminergic system.

  7. 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

  8. ATP-sensitive Potassium Channels and L-type Calcium Channels are Involved in Morphine-induced Hyperalgesia after Nociceptive Sensitization in Mice

    PubMed Central

    Ahmadi, Shamseddin; Azarian, Shaho; Ebrahimi, Sayede Shohre; Rezayof, Ameneh

    2014-01-01

    Introduction We investigated the role of ATP-sensitive potassium channels and L-type calcium channels in morphine-induced hyperalgesia after nociceptive sensitization. Methods We used a hotplate apparatus to assess pain behavior in male NMRI mice. Nociceptive sensitization was induced by three days injection of morphine and five days of drug free. On day 9 of the schedule, pain behavior test was performed for evaluating the effects of morphine by itself and along with nimodipine, a blocker of L-type calcium channels and diazoxide, an opener of ATP-sensitive potassium channels. All drugs were injected through an intraperitoneal route. Results The results showed that morphine (7.5, 10 and 15 mg/kg) induced analgesia in normal mice, which was prevented by naloxone (1 mg/kg). After nociceptive sensitization, analgesic effect of morphine (10 and 15 mg/kg) was significantly decreased in sensitized mice. The results showed that nimodipine (2.5, 5, 10 and 20 mg/kg) had no significant effect on pain behavior test in either normal or sensitized mice. However, nimodipine (20 mg/ kg) along with morphine (10 and 15 mg/kg) caused more decrease in morphine analgesia in sensitized mice. Furthermore, diazoxide by itself (0.25, 1, 5 and 20 mg/kg) had also no significant effect on pain behavior in both normal and sensitized mice, but at dose of 20 mg/kg along with morphine (10 and 15 mg/kg) decreased analgesic effect of morphine in sensitized mice. Discussion It can be concluded that potassium and calcium channels have some roles in decrease of analgesic effect of morphine after nociceptive sensitization induced by pretreatment of morphine. PMID:25337379

  9. 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

    2016-06-02

    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

  10. 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.

  11. Inhibition of spinal ERK1/2-c-JUN signaling pathway counteracts the development of low doses morphine-induced hyperalgesia.

    PubMed

    Sanna, Maria Domenica; Mello, Tommaso; Ghelardini, Carla; Galeotti, Nicoletta

    2015-10-05

    Morphine-induced hyperalgesia is a pharmacological phenomenon often hindering its prolonged applications in the clinic. It has been shown that systemic administration of morphine induced a hyperalgesic response at an extremely low dose. Extracellular signal-regulated kinase (ERK) pathway contributes to pain sensitization, and its phosphorylation under pain conditions results in the induction and maintenance of pain hypersensitivity. The present study was designed to determine whether low dose morphine treatment in mice could influence the spinal activity of ERK. The data showed that morphine (1 µg/kg) induced a marked increase in ERK phosphorylation. Intrathecal pre-treatment with a selective mitogen-activated and extracellular signal-regulated kinase (MEK) inhibitor PD98059, attenuated morphine-associated thermal hyperalgesia. Morphine exposure increased phosphorylation of c-JUN, that was prevented by the inhibition of ERK pathway. In addition, double immunofluorescence studies revealed that, p-ERK and p-c-JUN are localized on neurons of the spinal dorsal horn expressing µ receptors. These data suggest that ERK contributes to the morphine-induced hyperalgesia by regulating the activation of c-JUN.

  12. 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

  13. 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.

  14. 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

  15. Toll-like Receptor 4 Mediates Morphine-Induced Neuroinflammation and Tolerance via Soluble Tumor Necrosis Factor Signaling.

    PubMed

    Eidson, Lori N; Inoue, Kiyoshi; Young, Larry J; Tansey, Malu G; Murphy, Anne Z

    2017-02-01

    Opioid tolerance and the potential for addiction is a significant burden associated with pain management, yet its precise underlying mechanism and prevention remain elusive. Immune signaling contributes to the decreased efficacy of opioids, and we recently demonstrated that Toll-like receptor 4 (TLR4)-mediated neuroinflammation in the periaqueductal gray (PAG) drives tolerance. Tumor necrosis factor (TNF), a product of TLR4 signaling, promotes inflammation and facilitates glutamatergic signaling, key components of opioid tolerance. Therefore, we hypothesize that TLR4-mediated opioid tolerance requires TNF signaling. By expression of a dominant-negative TNF peptide via lentiviral vector injection in rat PAG to sequester soluble TNF (solTNF), we demonstrate that solTNF mediates morphine tolerance induced by TLR4 signaling, stimulates neuroinflammation (increased IL-1β and TLR4 mRNA), and disrupts glutamate reuptake (decreased GLT-1 and GLAST mRNA). We further demonstrate the efficacy of the brain-permeant PEGylated version of the anti-solTNF peptide, XPro1595, injected systemically, to normalize morphine-induced CNS neuroinflammation and morphine- and endotoxin-induced changes in glutamate transport, effectively preserving the efficacy of morphine analgesia and eliminating tolerance. Our findings provide a novel pharmacological target for the prevention of opioid-induced immune signaling, tolerance, and addiction.

  16. 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

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

    PubMed

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

    2011-12-23

    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.

  18. Effects of MPEP on locomotion, sensitization and conditioned reward induced by cocaine or morphine.

    PubMed

    Herzig, Volker; Schmidt, Werner J

    2004-12-01

    Exposure to environmental cues is considered a major cause of relapse in detoxified addicts. Recent findings showed an involvement of glutamate in cue-induced relapse and suggest that subtype 5 of metabotropic glutamate receptors (mGluR5) is involved in conditioned drug-reward. The present study applied the conditioned place preference (CPP) paradigm to examine the involvement of mGluR5 in cocaine- and morphine-induced behaviours. Results of previous mice-studies were extended into rats by using the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP). As a result, the evaluated behavioural parameters were dose-relatedly affected by MPEP. Low-dosed MPEP (10 mg/kg, i.p.) did not affect spontaneous locomotion, reduced cocaine-induced hyperlocomotion and produced sensitized locomotion, while showing no effect on sensitized locomotion induced by repeated cocaine or morphine. Low-dosed MPEP did not genuinely block development of cocaine- and morphine-CPP, but rendered CPP expression state-dependent. The medium MPEP-dose (30 mg/kg) was most effective in reducing spontaneous locomotion. The high MPEP-dose (50 mg/kg) was most effective in reducing both body-weight and morphine-CPP expression. Cocaine-CPP expression was not affected by any MPEP-dose. In conclusion, mGluR5 are involved in modulation of spontaneous and cocaine-induced locomotion, in state-dependent learning and in expression of morphine-CPP. Thus, MPEP may be beneficial for relapse prevention in morphine-addicts.

  19. 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

  20. 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.

  1. Incentive theory: IV. Magnitude of reward

    PubMed Central

    Killeen, Peter R.

    1985-01-01

    Incentive theory is successfully applied to data from experiments in which the amount of food reward is varied. This is accomplished by assuming that incentive value is a negatively accelerated function of reward duration. The interaction of the magnitude of a reward with its delay is confirmed, and the causes and implications of this interaction are discussed. PMID:16812421

  2. 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.

  3. NMDA receptors of dorsal hippocampus are involved in the acquisition, but not in the expression of morphine-induced place preference.

    PubMed

    Zarrindast, Mohammad-Reza; Lashgari, Reza; Rezayof, Ameneh; Motamedi, Fereshteh; Nazari-Serenjeh, Farzaneh

    2007-07-30

    In the present study, involvement of the N-methyl-d-aspartate (NMDA) receptors of the CA1 region of dorsal hippocampus (intra-CA1) in the acquisition or expression of morphine-induced conditioned place preference in rats was studied. Male Wistar rats were used in these experiments. NMDA-receptor agonist (NMDA) and antagonist (MK-801) were injected into the CA1 region of the dorsal hippocampus (intra-CA1) and morphine was injected subcutaneously. An unbiased conditioned place preference paradigm was used to study the effect of these agents. In the first set of experiments, the drugs were used during the development of conditioned place preference by morphine or they were used alone in order to see if they induce conditioned place preference or conditioned place aversion. Our data showed that subcutaneous (s.c.) injection of morphine sulphate (2.5-10 mg/kg) induced conditioned place preference in rat. NMDA (0.1-1 microg/rat) or MK-801 (1-4 microg/rat) did not induce conditioned place preference or conditioned place aversion. Intra-CA1 administration of different doses of NMDA (0.1-1 microg/rat) increased, while MK-801 (1-4 microg/rat) decreased morphine-induced place preference. MK-801 reversed the effect of NMDA on morphine response. In the second set of experiments, when the drugs were used before testing on Day 5, in order to test their effects on the expression of morphine (7.5 mg/kg)-induced place preference, intra-CA1 administration of NMDA or MK-801 did not alter the morphine response. None of the drugs influenced locomotion. It is concluded that NMDA receptor of the CA1 region of hippocampus are involved in the acquisition but not expression of morphine-induced place preference.

  4. Yohimbine prevents morphine-induced changes of glial fibrillary acidic protein in brainstem and alpha2-adrenoceptor gene expression in hippocampus.

    PubMed

    Alonso, Elba; Garrido, Elisa; Díez-Fernández, Carmen; Pérez-García, Carmen; Herradón, Gonzalo; Ezquerra, Laura; Deuel, Thomas F; Alguacil, Luis F

    2007-01-29

    The alpha(2)-adrenoceptor antagonist yohimbine is known to oppose to several pharmacological effects of opioid drugs, but the consequences and the mechanisms involved remain to be clearly established. In the present study we have checked the effects of yohimbine on morphine-induced alterations of the expression of key proteins (glial fibrillary acidic protein, GFAP) and genes (alpha(2)-adrenoceptors) in rat brain areas known to be relevant in opioid dependence, addiction and individual vulnerability to drug abuse. Rats were treated with morphine in the presence or absence of yohimbine. The effects of the treatments on GFAP expression were studied by immunohistochemical staining in Locus Coeruleus (LC) and Nucleus of the Solitary Tract (NST), two important noradrenergic nuclei. In addition, drug effects on alpha(2)-adrenoceptor gene expression were determined by real time RT-PCR in the hippocampus, a brain area that receives noradrenergic input from the brainstem. Morphine administration increased GFAP expression both in LC and NST as it was previously reported in other brain areas. Yohimbine was found to efficiently prevent morphine-induced GFAP upregulation. Chronic (but not acute) morphine downregulated mRNA levels of alpha(2A)- and alpha(2C)-adrenoceptors in the hippocampus, while simultaneously increased the expression of the alpha(2B)-adrenoceptor gene. Again, yohimbine was able to prevent morphine-induced changes in the levels of expression of the three alpha(2)-adrenoceptor genes. These results correlate the well-established reduction of opioid dependence and addiction by yohimbine and suggest that this drug could interfere with the neural plasticity induced by chronic morphine in central noradrenergic pathways.

  5. Establishment of opioid-induced rewarding effects under oxaliplatin- and Paclitaxel-induced neuropathy in rats.

    PubMed

    Mori, Tomohisa; Kanbara, Tomoe; Harumiya, Masato; Iwase, Yoshiyuki; Masumoto, Aki; Komiya, Sachiko; Nakamura, Atsushi; Shibasaki, Masahiro; Kanemasa, Toshiyuki; Sakaguchi, Gaku; Suzuki, Tsutomu

    2014-01-01

    The rewarding effects of μ-receptor agonists can be suppressed under several pain conditions. We recently showed that clinically used μ-receptor agonists possess efficacies for relieving the neuropathic pain induced by chemotherapeutic drug in rats; however, it is possible that the use of μ-receptor agonists may trigger the rewarding effects even under chemotherapeutic drug-induced neuropathic pain. Nevertheless, no information is available regarding whether μ-receptor agonists produce psychological dependence under chemotherapeutic drug-induced neuropathic pain. Therefore, we examined the effects of neuropathy induced by chemotherapeutic drugs on the rewarding effects of morphine, oxycodone, and fentanyl in rats. Repeated treatment with oxaliplatin or paclitaxel produced neuropathy as measured by the von Frey test. Rewarding effects produced by antinociceptive doses of μ-receptor agonists were not suppressed under oxaliplatin- or paclitaxel-induced neuropathy. Furthermore, the morphine-induced increase in the release of dopamine from the nucleus accumbens, which is a critical step in the rewarding effects of μ-receptor agonists, was not altered in paclitaxel-treated rats. These results suggest that the rewarding effects of μ-receptor agonists can still be established under oxaliplatin- or paclitaxel-induced neuropathic pain. Therefore, patients should be carefully monitored for psychological dependence on μ-receptor agonists when they are used to control chemotherapeutic drug-induced neuropathic pain.

  6. Acute morphine induces matrix metalloproteinase-9 up-regulation in primary sensory neurons to mask opioid-induced analgesia in mice

    PubMed Central

    2012-01-01

    Background Despite decades of intense research efforts, actions of acute opioids are not fully understood. Increasing evidence suggests that in addition to well-documented antinociceptive effects opioids also produce paradoxical hyperalgesic and excitatory effects on neurons. However, most studies focus on the pronociceptive actions of chronic opioid exposure. Matrix metalloproteinase 9 (MMP-9) plays an important role in neuroinflammation and neuropathic pain development. We examined MMP-9 expression and localization in dorsal root ganglia (DRGs) after acute morphine treatment and, furthermore, the role of MMP-9 in modulating acute morphine-induced analgesia and hyperalgesia in mice. Results Subcutaneous morphine induced a marked up-regulation of MMP-9 protein in DRGs but not spinal cords. Morphine also increased MMP-9 activity and mRNA expression in DRGs. MMP-9 up-regulation peaked at 2 h but returned to the baseline after 24 h. In DRG tissue sections, MMP-9 is expressed in small and medium-sized neurons that co-express mu opioid receptors (MOR). In DRG cultures, MOR agonists morphine, DAMGO, and remifentanil each increased MMP-9 expression in neurons, whereas the opioid receptor antagonist naloxone and the MOR-selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) suppressed morphine-induced MMP-9 expression. Notably, subcutaneous morphine-induced analgesia was enhanced and prolonged in Mmp9 knockout mice and also potentiated in wild-type mice receiving intrathecal injection of MMP-9 inhibitors. Consistently, intrathecal injection of specific siRNA targeting MMP-9 reduced MMP-9 expression in DRGs and enhanced and prolonged morphine analgesia. Subcutaneous morphine also produced heat hyperalgesia at 24 h, but this opioid-induced hyperalgesia was not enhanced after MMP-9 deletion or inhibition. Conclusions Transient MMP-9 up-regulation in DRG neurons can mask opioid analgesia, without modulating opioid-induced hyperalgesia. Distinct molecular

  7. Genetic and environmental causes of individual differences in daily life positive affect and reward experience and its overlap with stress-sensitivity.

    PubMed

    Menne-Lothmann, Claudia; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Wichers, Marieke

    2012-09-01

    Momentary positive affect (PA) and reward experience may underlie subjective wellbeing, and index mental health resilience. This study examines their underlying sources of variation and the covariation with stress-sensitivity. The experience sampling method was used to collect multiple appraisals of mood and daily life events in 520 female twins. Structural equation model fitting was employed to determine sources of variation of PA, reward experience, and the association between reward experience and stress-sensitivity. PA was best explained by shared and non-shared environmental factors, and reward experience by non-shared environmental factors only, although the evidence was also suggestive of a small genetic contribution. Reward experience and stress-sensitivity showed no association. PA was not heritable. Most-if not all-variance of reward experience was explained by environmental influences. Stress-sensitivity, indexing depression vulnerability, and reward experience were non-overlapping, suggesting that resilience traits are independent from stress-sensitivity levels in a general population sample.

  8. Post-Transcriptional Regulation of the Human Mu-Opioid Receptor (MOR) by Morphine-Induced RNA Binding Proteins hnRNP K and PCBP1

    PubMed Central

    Song, Kyu Young; Choi, Hack Sun; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H.

    2016-01-01

    Expression of the mu-opioid receptor (MOR) protein is controlled by extensive transcriptional and post-transcriptional processing. MOR gene expression has previously been shown to be altered by a post-transcriptional mechanism involving the MOR mRNA untranslated region (UTR). Here, we demonstrate for the first time the role of heterogeneous nuclear ribonucleic acids (hnRNA)-binding protein (hnRNP) K and poly(C)-binding protein 1 (PCBP1) as post-transcriptional inducers in MOR gene regulation. In the absence of morphine, a significant level of MOR mRNA is sustained in its resting state and partitions in the translationally inactive polysomal fraction. Morphine stimulation activates the downstream targets hnRNP K and PCPB1 and induces partitioning of the MOR mRNA to the translationally active fraction. Using reporter and ligand binding assays, as well as RNA EMSA, we reveal potential RNP binding sites located in the 5′-untranslated region of human MOR mRNA. In addition, we also found that morphine-induced RNPs could regulate MOR expression. Our results establish the role of hnRNP K and PCPB1 in the translational control of morphine-induced MOR expression in human neuroblastoma (NMB) cells as well as cells stably expressing MOR (NMB1). PMID:27292014

  9. Dopamine D₄ receptor counteracts morphine-induced changes in µ opioid receptor signaling in the striosomes of the rat caudate putamen.

    PubMed

    Suárez-Boomgaard, Diana; Gago, Belén; Valderrama-Carvajal, Alejandra; Roales-Buján, Ruth; Van Craenenbroeck, Kathleen; Duchou, Jolien; Borroto-Escuela, Dasiel O; Medina-Luque, José; de la Calle, Adelaida; Fuxe, Kjell; Rivera, Alicia

    2014-01-21

    The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [35S]GTPγS autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to Gi/0 protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine.

  10. Supraspinal Gβγ-dependent stimulation of PLCβ3 originating from G inhibitory protein-μ opioid receptor-coupling is necessary for morphine induced acute hyperalgesia

    PubMed Central

    Bianchi, Enrica; Norcini, Monica; Smrcka, Alan; Ghelardini, Carla

    2009-01-01

    Although alterations in μ-opioid receptor signaling mediate excitatory effects of opiates in opioid tolerance, the molecular mechanism for the excitatory effect of acute low dose morphine, as it relates to μ-opioid receptor coupling, is presently unknown. A pronounced coupling of μ-opioid receptor to the α subunit of G inhibitory protein emerged in periaqueductal gray from mice systemically administered with morphine at a dose producing acute thermal hyperalgesia. This coupling was abolished in presence of the selective μ-opioid receptor receptor antagonist CTOP administered at the periaqueductal gray site, showing that the low dose morphine effect is triggered by μ-opioid receptor activated G inhibitory protein at supraspinal level. When Gβγ downstream signalling was blocked by intra-periaqueductal gray co-administration of M119, a compound that inhibits Gβγ dimer-dependent signaling, a complete prevention of low dose morphine induced acute thermal hyperalgesia was obtained. Phospholipase C β3, an enzyme necessary to morphine hyperalgesia, was revealed to be associated with Gβγ in periaqueductal gray. Although opioid administration induces a shift in μ-opioid receptor-G protein coupling from Gi to Gs after chronic administration, our data support that this condition is not realized in acute treatment providing evidence that a separate molecular mechanism underlies morphine induced acute excitatory effect. PMID:19656263

  11. Post-Transcriptional Regulation of the Human Mu-Opioid Receptor (MOR) by Morphine-Induced RNA Binding Proteins hnRNP K and PCBP1.

    PubMed

    Song, Kyu Young; Choi, Hack Sun; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H

    2017-03-01

    Expression of the mu-opioid receptor (MOR) protein is controlled by extensive transcriptional and post-transcriptional processing. MOR gene expression has previously been shown to be altered by a post-transcriptional mechanism involving the MOR mRNA untranslated region (UTR). Here, we demonstrate for the first time the role of heterogeneous nuclear ribonucleic acids (hnRNA)-binding protein (hnRNP) K and poly(C)-binding protein 1 (PCBP1) as post-transcriptional inducers in MOR gene regulation. In the absence of morphine, a significant level of MOR mRNA is sustained in its resting state and partitions in the translationally inactive polysomal fraction. Morphine stimulation activates the downstream targets hnRNP K and PCPB1 and induces partitioning of the MOR mRNA to the translationally active fraction. Using reporter and ligand binding assays, as well as RNA EMSA, we reveal potential RNP binding sites located in the 5'-untranslated region of human MOR mRNA. In addition, we also found that morphine-induced RNPs could regulate MOR expression. Our results establish the role of hnRNP K and PCPB1 in the translational control of morphine-induced MOR expression in human neuroblastoma (NMB) cells as well as cells stably expressing MOR (NMB1). J. Cell. Physiol. 232: 576-584, 2017. © 2016 Wiley Periodicals, Inc.

  12. 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

  13. 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

    2016-08-04

    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

  14. 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

  15. 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

  16. 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

  17. 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…

  18. Inhibitory effects of SA4503 on the rewarding effects of abused drugs.

    PubMed

    Mori, Tomohisa; Rahmadi, Mahardian; Yoshizawa, Kazumi; Itoh, Toshimasa; Shibasaki, Masahiro; Suzuki, Tsutomu

    2014-05-01

    Previous findings have shown that sigma-1 receptors (Sig-1Rs) are upregulated by the self-administration of methamphetamine, whereas Sig-1R antisense can attenuate the behavioral effects of psychostimulants in rodents. Sig-1R is an endoplasmic reticulum chaperone protein. However, the effects of Sig-1R agonist on the rewarding effects of abused drugs are not fully understood. Therefore, we examined the effects of selective Sig-1R agonists, such as SA4503 and (+)-pentazocine, on the rewarding effects of abused drugs such as methamphetamine, cocaine and morphine in rats, as measured by the conditioned place preference. Methamphetamine, cocaine and morphine induced a significant place preference. SA4503, but not (+)-pentazocine, significantly attenuated the abused drug-induced place preference. We recently showed that (+)-pentazocine exerts U50,488H-like discriminative stimulus effects, which are related to its psychotomimetic/aversive effects. However, SA4503 did not generalize to the discriminative stimulus effects of U50,488H. These results suggest that SA4503 inhibits the rewarding effects of abused drugs, and that psychotomimetic/aversive effects may not play a role in the attenuating effects of SA4503 on the rewarding effects of abused drugs.

  19. 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

  20. 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

    2016-02-26

    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.

  1. The role of nitric oxide in the effects of cumin (Cuminum Cyminum L.) fruit essential oil on the acquisition of morphine-induced conditioned place preference in adult male mice.

    PubMed

    Kermani, Mojtaba; Azizi, Pegah; Haghparast, Abbas

    2012-01-12

    OBJECTIVE: Nitric oxide is a neural messenger molecule in the central nervous system that is generated from L-arginine via the nitric oxide synthase (NOS) and is involved in many important oplold-induced effects. In Iranian ancient medicine, Cuminum cyminum L (green seed) has been used for the treatment of some diseases. In the present study, the effect of intraperitoneal (ip) administration of different doses of cumin fruit essential oil (FEO) on the acquisition of morphine-induced conditioned place preference (GPP) in L-arginine-treated mice was investigated. METHODS: A total of 213 adult male albino Wistar mice were used in these experiments. The CPP paradigm was carried out in 5 continuous days, pre-conditioning, conditioning and post-conditioning. Animals were randomly assigned to one of the two groups for place conditioning. CPP was induced by subcutaneous (sc) injection of morphine (5 mg/kg) in 3 days conditioning schedule. On the test day, conditioning scores and locomotor activity were recorded by Ethovision software. RESULTS: Sole administration of different doses of cumin FEO (0.01%, 0.1%, 0.5%, 1% and 2%; lp) or L-arginine (50, 100 and 200 mg/kg; lp) during the CPP protocol could not induce CPP. Nonetheless, morphine-induced CPP was decreased by different doses of cumin FEO (0.01%-2%), whereas it was increased by L-arginine (50-200 mg/kg) when they were injected before morphine (5 rug/kg) during a 3-day conditioning phase (acquisition period). Additionally, cumin FEO could interestingly attenuate the raising effect of L-arginine on morphine-induced CPP in a dose-dependent manner. CONCLUSIONS: It is suggested that some components of the Cuminum cyminum L. seed attenuate the excessive effect of L-arginine on morphine-induced CPP through the NOS inhibitory mechanism. It seems that cumin FEO possibly acts as a NOS inhibitor.

  2. Punished by Rewards?

    ERIC Educational Resources Information Center

    Brandt, Ron

    1995-01-01

    The author of "Punished by Rewards" (1993), claims that rewards and punishments serve to manipulate behavior and destroy the potential for real learning. Praise is especially tricky, since intangible rewards can also foster compliance, not motivation. An engaging curriculum and a caring atmosphere encourage kids to exercise their natural…

  3. MeCP2 repression of G9a in regulation of pain and morphine reward.

    PubMed

    Zhang, Zhi; Tao, Wenjuan; Hou, Yuan-Yuan; Wang, Wei; Kenny, Paul J; Pan, Zhizhong Z

    2014-07-02

    Opioids are commonly used for pain relief, but their strong rewarding effects drive opioid misuse and abuse. How pain affects the liability of opioid abuse is unknown at present. In this study, we identified an epigenetic regulating cascade activated by both pain and the opioid morphine. Both persistent pain and repeated morphine upregulated the transcriptional regulator MeCP2 in mouse central nucleus of the amygdala (CeA). Chromatin immunoprecipitation analysis revealed that MeCP2 bound to and repressed the transcriptional repressor histone dimethyltransferase G9a, reducing G9a-catalyzed repressive mark H3K9me2 in CeA. Repression of G9a activity increased expression of brain-derived neurotrophic factor (BDNF). Behaviorally, persistent inflammatory pain increased the sensitivity to acquiring morphine-induced, reward-related behavior of conditioned place preference in mice. Local viral vector-mediated MeCP2 overexpression, Cre-induced G9a knockdown, and CeA application of BDNF mimicked, whereas MeCP2 knockdown inhibited, the pain effect. These results suggest that MeCP2 directly represses G9a as a shared mechanism in central amygdala for regulation of emotional responses to pain and opioid reward, and for their behavioral interaction.

  4. MeCP2 Repression of G9a in Regulation of Pain and Morphine Reward

    PubMed Central

    Zhang, Zhi; Tao, Wenjuan; Hou, Yuan-Yuan; Wang, Wei; Kenny, Paul J.

    2014-01-01

    Opioids are commonly used for pain relief, but their strong rewarding effects drive opioid misuse and abuse. How pain affects the liability of opioid abuse is unknown at present. In this study, we identified an epigenetic regulating cascade activated by both pain and the opioid morphine. Both persistent pain and repeated morphine upregulated the transcriptional regulator MeCP2 in mouse central nucleus of the amygdala (CeA). Chromatin immunoprecipitation analysis revealed that MeCP2 bound to and repressed the transcriptional repressor histone dimethyltransferase G9a, reducing G9a-catalyzed repressive mark H3K9me2 in CeA. Repression of G9a activity increased expression of brain-derived neurotrophic factor (BDNF). Behaviorally, persistent inflammatory pain increased the sensitivity to acquiring morphine-induced, reward-related behavior of conditioned place preference in mice. Local viral vector-mediated MeCP2 overexpression, Cre-induced G9a knockdown, and CeA application of BDNF mimicked, whereas MeCP2 knockdown inhibited, the pain effect. These results suggest that MeCP2 directly represses G9a as a shared mechanism in central amygdala for regulation of emotional responses to pain and opioid reward, and for their behavioral interaction. PMID:24990928

  5. 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.

  6. 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

  7. 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

  8. 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…

  9. Dopamine reward prediction error coding.

    PubMed

    Schultz, Wolfram

    2016-03-01

    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.

  10. Reward expectations in honeybees.

    PubMed

    Gil, Mariana

    2010-03-01

    The study of expectations of reward helps to understand rules controlling goal-directed behavior as well as decision making and planning. I shall review a series of recent studies focusing on how the food gathering behavior of honeybees depends upon reward expectations. These studies document that free-flying honeybees develop long-term expectations of reward and use them to regulate their investment of energy/time during foraging. Also, they present a laboratory procedure suitable for analysis of neural substrates of reward expectations in the honeybee brain. I discuss these findings in the context of individual and collective foraging, on the one hand, and neurobiology of learning and memory of reward.

  11. 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.

  12. ABCC3 Genetic Variants are Associated with Postoperative Morphine-induced Respiratory Depression and Morphine Pharmacokinetics in Children

    PubMed Central

    Chidambaran, Vidya; Venkatasubramanian, Raja; Zhang, Xue; Martin, Lisa J.; Niu, Jing; Mizuno, Tomoyuki; Fukuda, Tsuyoshi; Meller, Jaroslaw; Vinks, Alexander A.; Sadhasivam, Senthilkumar

    2015-01-01

    Respiratory depression (RD) is a serious side effect of morphine and detrimental to effective analgesia. We reported that variants of the ATP binding cassette gene ABCC3 (facilitates hepatic morphine metabolite efflux), affect morphine metabolite clearance. In this study of 316 children undergoing tonsillectomy, we found significant association between ABCC3 variants and RD leading to prolonged postoperative care unit stay (Prolonged RD). Allele A at rs4148412 and allele G at rs729923 caused a 2.36 (95% CI=1.28–4.37, p=0.0061) and 3.7 (95% CI 1.47– 9.09, p=0.0050) times increase in odds of Prolonged RD respectively. These clinical associations were supported by increased formation clearance of morphine glucuronides in children with rs4148412 AA and rs4973665 CC genotypes in this cohort, as well as an independent spine surgical cohort of 67 adolescents. This is the first study to report association of ABCC3 variants with opioid -related RD, and morphine metabolite formation (in two independent surgical cohorts). PMID:26810133

  13. 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

  14. A Growth Factor Attenuates HIV-1 Tat and Morphine Induced Damage to Human Neurons: Implication in HIV/AIDS-Drug Abuse Cases

    PubMed Central

    Malik, Shaily; Khalique, Hena; Buch, Shilpa; Seth, Pankaj

    2011-01-01

    The neuropathological abnormalities of human immunodeficiency virus (HIV)-1 patients abusing illicit drugs suggest extensive interactions between the two agents, thereby leading to increased rate of progression to neurodegeneration. The role of HIV-1 transactivating protein, Tat has been elucidated in mediating neuronal damage via apoptosis, a hallmark of HIV-associated dementia (HAD), however the underlying mechanisms involved in enhanced neurodegeneration by illicit drugs remain elusive. In this study, we demonstrated that morphine enhances HIV-Tat induced toxicity in human neurons and neuroblastoma cells. Enhanced toxicity by Tat and morphine was accompanied by increased numbers of TUNEL positive apoptotic neurons, elevated caspase-3 levels and decreased ratio of anti- and pro-apoptotic proteins, Bcl2/Bax. Tat and morphine together elicited high levels of reactive oxygen species that were NADPH dependent. Significant alterations in mitochondrial membrane homeostasis were also observed with co-exposure of these agents. Extensive studies of mitogen activated protein kinase (MAPK) signaling pathways revealed the involvement of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase-1/2 (ERK1/2) pathways in enhanced toxicity of Tat and morphine. In addition to this, we found that pre-treatment of cells with platelet derived growth factor (PDGF-BB) protected neurons from HIV-Tat and morphine induced damage. PDGF-BB alleviated ROS production, maintained mitochondrial membrane potential, decreased caspase-3 activation and hence protected the cells from undergoing apoptosis. PDGF-BB mediated protection against Tat and morphine involved the phosphatidylinositol–3 kinase (PI3K) pathway, as specific inhibitor of PI3K abrogated the protection conferred by PDGF-BB. This study demonstrates the mechanism of enhanced toxicity in human neurons subjected to co-exposure of HIV protein Tat and morphine, thus implying its importance in HIV positive drug abusers

  15. Reducing endocannabinoid metabolism with the fatty acid amide hydrolase inhibitor, URB597, fails to modify reinstatement of morphine-induced conditioned floor preference and naloxone-precipitated morphine withdrawal-induced conditioned floor avoidance.

    PubMed

    McCallum, Amanda L; Limebeer, Cheryl L; Parker, Linda A

    2010-10-01

    The potential of the fatty acid amide hydrolase (FAAH) inhibitor, URB597, to modify drug prime-induced reinstatement of morphine-induced conditioned floor preference or naloxone-precipitated morphine withdrawal-induced conditioned floor avoidance was evaluated. In Experiment 1, morphine-induced conditioned floor preference was established across 4 conditioning trials. Following extinction training (4 trials), rats were pretreated with URB597 or vehicle prior to a morphine prime or a saline prime. Morphine reinstated the previously extinguished floor preference, but URB597 did not modify the strength of the reinstated preference. In Experiment 2, naloxone-precipitated morphine withdrawal-induced conditioned floor avoidance was established across 2 conditioning trials. Following extinction training (14 trials), rats were pretreated with URB597 or vehicle prior to a saline prime or a morphine withdrawal prime. The morphine withdrawal prime reinstated the previously extinguished floor avoidance, but URB597 did not modify the strength of reinstated avoidance. These results suggest that under the conditions in which URB597 promotes extinction (e.g., Manwell et al. (2009)) it does not interfere with drug-induced reinstatement of either conditioned floor preference or avoidance. That is, although activation of the endocannabinoid (eCB) system promotes extinction of aversive learning, it may not prevent reinstatement of that aversion by re-exposure to the aversive treatment.

  16. Reward, context, and human behaviour.

    PubMed

    Blaukopf, Clare L; DiGirolamo, Gregory J

    2007-05-29

    Animal models of reward processing have revealed an extensive network of brain areas that process different aspects of reward, from expectation and prediction to calculation of relative value. These results have been confirmed and extended in human neuroimaging to encompass secondary rewards more unique to humans, such as money. The majority of the extant literature covers the brain areas associated with rewards whilst neglecting analysis of the actual behaviours that these rewards generate. This review strives to redress this imbalance by illustrating the importance of looking at the behavioural outcome of rewards and the context in which they are produced. Following a brief review of the literature of reward-related activity in the brain, we examine the effect of reward context on actions. These studies reveal how the presence of reward vs. reward and punishment, or being conscious vs. unconscious of reward-related actions, differentially influence behaviour. The latter finding is of particular importance given the extent to which animal models are used in understanding the reward systems of the human mind. It is clear that further studies are needed to learn about the human reaction to reward in its entirety, including any distinctions between conscious and unconscious behaviours. We propose that studies of reward entail a measure of the animal's (human or nonhuman) knowledge of the reward and knowledge of its own behavioural outcome to achieve that reward.

  17. Exposure to Opiates in Female Adolescents Alters Mu Opiate Receptor Expression and Increases the Rewarding Effects of Morphine in Future Offspring

    PubMed Central

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

    2016-01-01

    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

  18. 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.

  19. Reward modulates adaptations to conflict.

    PubMed

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

    2012-11-01

    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 flanker task (Experiment 1) or a task-switch paradigm (Experiment 2) with performance-related rewards. Both experiments confirmed that adaptations after conflict were modulated by reward. In the flanker task, this resulted in increased conflict adaptation after rewarded trials. In the task-switching experiment, reward increased the conflict-modulated switch cost. Interestingly, both adaptations to conflict disappeared after no-reward trials. Moreover, individual differences in participants' sensitivity to reward predicted these reward modulations of trial-to-trial adaptations. These findings shed new light on the exact role of cognitive conflict in shaping subsequent behavior.

  20. Updating dopamine reward signals

    PubMed Central

    Schultz, Wolfram

    2013-01-01

    Recent work has advanced our knowledge of phasic dopamine reward prediction error signals. The error signal is bidirectional, reflects well the higher order prediction error described by temporal difference learning models, is compatible with model-free and model-based reinforcement learning, reports the subjective rather than physical reward value during temporal discounting and reflects subjective stimulus perception rather than physical stimulus aspects. Dopamine activations are primarily driven by reward, and to some extent risk, whereas punishment and salience have only limited activating effects when appropriate controls are respected. The signal is homogeneous in terms of time course but heterogeneous in many other aspects. It is essential for synaptic plasticity and a range of behavioural learning situations. PMID:23267662

  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.

  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. 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…

  4. Bribes or Rewards.

    ERIC Educational Resources Information Center

    Megyeri, Kathy A.

    Small tangible rewards for student progress, such as candy bars, pens, or ribbons, add potency to the verbal and written praise offered by the teacher, thus increasing student motivation. Giving students small prizes enhances the cooperative atmosphere of learning, especially for those who do not normally do well. Research indicates that low…

  5. 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…

  6. Rewards and Supports

    ERIC Educational Resources Information Center

    Hershberg, Theodore; Robertson-Kraft, Claire

    2010-01-01

    Pay-for-performance systems in public schools have long been burdened with controversy. Critics of performance pay systems contend that because teachers' impact cannot be measured without error, it is impossible to create fair and accurate systems for evaluating and rewarding performance. By this standard, however, current practice fails on both…

  7. Performance Management and Reward

    NASA Astrophysics Data System (ADS)

    Yiannis, Triantafyllopoulos; Ioannis, Seimenis; Nikolaos, Konstantopoulos

    2009-08-01

    The article aims to examine, current Performance Management practices on Reward, financial or non-financial using lessons from the literature and the results of a qualitative analysis as these revealed from the interview of some executive members of Greek companies.

  8. Activation of Mas oncogene-related gene (Mrg) C receptors enhances morphine-induced analgesia through modulation of coupling of μ-opioid receptor to Gi-protein in rat spinal dorsal horn.

    PubMed

    Wang, D; Chen, T; Zhou, X; Couture, R; Hong, Y

    2013-12-03

    Mas oncogene-related gene (Mrg) G protein-coupled receptors are exclusively expressed in small-sized neurons in trigeminal and dorsal root ganglia (DRG) in mammals. The present study investigated the effect of MrgC receptor activation on morphine analgesic potency and addressed its possible mechanisms. Intrathecal (i.t.) administration of the specific MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22, 3 nmol) increased morphine-induced analgesia and shifted the morphine dose-response curve to the left in rats. Acute morphine (5 μg) reduced the coupling of μ-opioid receptors (MORs) to Gi-, but not Gs-, protein in the spinal dorsal horn. The i.t. BAM8-22 (3 nmol) prevented this change of G-protein repertoire while the inactive MrgC receptor agonist BAM8-18 (3 nmol, i.t.) failed to do so. A double labeling study showed the co-localization of MrgC and MORs in DRG neurons. The i.t. BAM8-22 also increased the coupling of MORs to Gi-protein and recruited Gi-protein from cytoplasm to the cell membrane in the spinal dorsal horn. Application of BAM8-22 (10nM) in the cultured ganglion explants for 30 min increased Gi-protein mRNA, but not Gs-protein mRNA. The present study demonstrated that acute administration of morphine inhibited the repertoire of MOR/Gi-protein coupling in the spinal dorsal horn in vivo. The findings highlight a novel mechanism by which the activation of MrgC receptors can modulate the coupling of MORs with Gi-protein to enhance morphine-induced analgesia. Hence, adjunct treatment of MrgC agonist BAM8-22 may be of therapeutic value to relieve pain.

  9. Differences in basal and morphine-induced FosB/DeltaFosB and pCREB immunoreactivities in dopaminergic brain regions of alcohol-preferring AA and alcohol-avoiding ANA rats.

    PubMed

    Kaste, Kristiina; Kivinummi, Tanja; Piepponen, T Petteri; Kiianmaa, Kalervo; Ahtee, Liisa

    2009-06-01

    Besides alcohol, alcohol-preferring AA and alcohol-avoiding ANA rats differ also with respect to other abused drugs. To study the molecular basis of these differences, we examined the expression of two transcription factors implicated in addiction, DeltaFosB and pCREB, in brain dopaminergic regions of AA and ANA rats. The effects of morphine and nicotine were studied to relate the behavioral and molecular changes induced by these drugs. Baseline FosB/DeltaFosB immunoreactivity (IR) in the nucleus accumbens core and pCREB IR in the prefrontal cortex (PFC) were elevated in AA rats. Morphine increased DeltaFosB-like IR more readily in the caudate-putamen of AA rats than in ANA rats. In the PFC morphine decreased pCREB IR in AA rats, but increased it in ANA rats. In addition to enhanced locomotor response, the development of place preference to morphine was enhanced in AA rats. The enhanced nicotine-induced locomotor sensitization found in AA compared with ANA rats seems to depend in addition to dopamine and DeltaFosB on other mechanisms. These findings suggest that enhanced sensitivity of AA rats to morphine is related to augmented morphine-induced expression of FosB/DeltaFosB and morphine-induced reduction of pCREB levels. Moreover, altered innate expression of FosB/DeltaFosB and pCREB in AA rats is likely to affect the sensitivity of these rats to abused drugs.

  10. 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

  11. Theory meets pigeons: the influence of reward-magnitude on discrimination-learning.

    PubMed

    Rose, Jonas; Schmidt, Robert; Grabemann, Marco; Güntürkün, Onur

    2009-03-02

    Modern theoretical accounts on reward-based learning are commonly based on reinforcement learning algorithms. Most noted in this context is the temporal-difference (TD) algorithm in which the difference between predicted and obtained reward, the prediction-error, serves as a learning signal. Consequently, larger rewards cause bigger prediction-errors and lead to faster learning than smaller rewards. Therefore, if animals employ a neural implementation of TD learning, reward-magnitude should affect learning in animals accordingly. Here we test this prediction by training pigeons on a simple color-discrimination task with two pairs of colors. In each pair, correct discrimination is rewarded; in pair one with a large-reward, in pair two with a small-reward. Pigeons acquired the 'large-reward' discrimination faster than the 'small-reward' discrimination. Animal behavior and an implementation of the TD-algorithm yielded comparable results with respect to the difference between learning curves in the large-reward and in the small-reward conditions. We conclude that the influence of reward-magnitude on the acquisition of a simple discrimination paradigm is accurately reflected by a TD implementation of reinforcement learning.

  12. High monetary reward rates and caloric rewards decrease temporal persistence

    PubMed Central

    Bode, Stefan; Murawski, Carsten

    2017-01-01

    Temporal persistence refers to an individual's capacity to wait for future rewards, while forgoing possible alternatives. This requires a trade-off between the potential value of delayed rewards and opportunity costs, and is relevant to many real-world decisions, such as dieting. Theoretical models have previously suggested that high monetary reward rates, or positive energy balance, may result in decreased temporal persistence. In our study, 50 fasted participants engaged in a temporal persistence task, incentivised with monetary rewards. In alternating blocks of this task, rewards were delivered at delays drawn randomly from distributions with either a lower or higher maximum reward rate. During some blocks participants received either a caloric drink or water. We used survival analysis to estimate participants' probability of quitting conditional on the delay distribution and the consumed liquid. Participants had a higher probability of quitting in blocks with the higher reward rate. Furthermore, participants who consumed the caloric drink had a higher probability of quitting than those who consumed water. Our results support the predictions from the theoretical models, and importantly, suggest that both higher monetary reward rates and physiologically relevant rewards can decrease temporal persistence, which is a crucial determinant for survival in many species. PMID:28228517

  13. 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.

  14. Nutritional controls of food reward.

    PubMed

    Fernandes, Maria F; Sharma, Sandeep; Hryhorczuk, Cecile; Auguste, Stephanie; Fulton, Stephanie

    2013-08-01

    The propensity to select and consume palatable nutrients is strongly influenced by the rewarding effects of food. Neural processes integrating reward, emotional states and decision-making can supersede satiety signals to promote excessive caloric intake and weight gain. While nutritional habits are influenced by reward-based neural mechanisms, nutrition and its impact on energy metabolism, in turn, plays an important role in the control of food reward. Feeding modulates the release of metabolic hormones that have an important influence on central controls of appetite. Nutrients themselves are also an essential source of energy fuel, while serving as key metabolites and acting as signalling molecules in the neural pathways that control feeding and food reward. Along these lines, this review discusses the impact of nutritionally regulated hormones and select macronutrients on the behavioural and neural processes underlying the rewarding effects of food.

  15. Rewarding with dignity.

    PubMed

    Davidhizar, R; Shearer, R

    1998-11-01

    Job satisfaction affects employee morale, which in turn affects employee productivity. Therefore, managers need to learn about contributing factors and use the factors within their power to improve job satisfaction. Extrinsic rewards, such as a high salary and good work benefits, are important, but studies show that how a job makes an employee feel is the greatest determinant of job satisfaction. Managers can influence the emotional effect of work on an employee through, among other strategies, recognizing the employee's efforts, providing opportunities for the employee to participate in decision making, and allowing the employee to grow professionally.

  16. 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

  17. Rewards teach visual selective attention.

    PubMed

    Chelazzi, Leonardo; Perlato, Andrea; Santandrea, Elisa; Della Libera, Chiara

    2013-06-07

    Visual selective attention is the brain function that modulates ongoing processing of retinal input in order for selected representations to gain privileged access to perceptual awareness and guide behavior. Enhanced analysis of currently relevant or otherwise salient information is often accompanied by suppressed processing of the less relevant or salient input. Recent findings indicate that rewards exert a powerful influence on the deployment of visual selective attention. Such influence takes different forms depending on the specific protocol adopted in the given study. In some cases, the prospect of earning a larger reward in relation to a specific stimulus or location biases attention accordingly in order to maximize overall gain. This is mediated by an effect of reward acting as a type of incentive motivation for the strategic control of attention. In contrast, reward delivery can directly alter the processing of specific stimuli by increasing their attentional priority, and this can be measured even when rewards are no longer involved, reflecting a form of reward-mediated attentional learning. As a further development, recent work demonstrates that rewards can affect attentional learning in dissociable ways depending on whether rewards are perceived as feedback on performance or instead are registered as random-like events occurring during task performance. Specifically, it appears that visual selective attention is shaped by two distinct reward-related learning mechanisms: one requiring active monitoring of performance and outcome, and a second one detecting the sheer association between objects in the environment (whether attended or ignored) and the more-or-less rewarding events that accompany them. Overall this emerging literature demonstrates unequivocally that rewards "teach" visual selective attention so that processing resources will be allocated to objects, features and locations which are likely to optimize the organism's interaction with the

  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. Rewards Are a Rat Trap.

    ERIC Educational Resources Information Center

    Maydosz, Ann S.

    1998-01-01

    Argues against the use of rewards for students. Discusses their origin in Skinner's behaviorism and their application in behavior modification in the classroom. Describes the problems with using rewards, as noted by Alfie Kohn and others, including the erosion of intrinsic motivation and the distortion of the focus of learning. Presents…

  20. 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).

  1. 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…

  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

    2016-04-06

    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.

  3. 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

  4. Developing a Comprehensive Reward System.

    ERIC Educational Resources Information Center

    Votruba, James C.

    1979-01-01

    Providing incentives for teachers of adults is an important means of attracting, retaining, and stimulating staff. Developing a variety of extrinsic and intrinsic rewards and incentives and instituting them effectively are important administrative functions. (SK)

  5. 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)

  6. Long-lasting changes in morphine-induced locomotor sensitization and tolerance in Long-Evans mother rats as a result of periodic postpartum separation from the litter: a novel model of increased vulnerability to drug abuse?

    PubMed

    Kalinichev, Mikhail; Easterling, Keith W; Holtzman, Stephen G

    2003-02-01

    Daily postpartum separations from the litter produce enduring changes in anxiety and sensitivity to the antinociceptive effects of morphine in Long-Evans dams. We tested whether postpartum experience alters sensitivity to the effects of morphine on locomotor activity. Dams were tested 4-6 weeks after their pups were weaned, and had one of the following backgrounds: daily separation from the litter on postpartum days 2-14 for either 3 h (prolonged separation-LS) or 15 min (brief separation-BS), or no separation (nonhandled control-NH). After 2 consecutive days (B1-2) of baseline activity measurements, subjects were tested daily after s.c. injections of either morphine (10 mg/kg) or saline for 7 days and again on day 10. Beginning 5 days later, saline and 1.0-10 mg/kg of morphine were tested in all dams. On B1, LS and BS dams habituated slower than NH controls, yielding higher horizontal counts. LS dams failed to habituate across baseline days and were more active than other dams on B2. Sensitization, a progressive increase in horizontal activity, was more rapid and robust in LS and BS dams compared to NH animals. LS was the only group that developed tolerance to morphine-induced decreases in vertical activity. In LS dams with the history of morphine treatment, injection of saline resulted in higher horizontal activity and center time compared to saline-treated counterparts, indicative of conditioning. Among animals with a history of saline treatment, LS dams were more sensitive to morphine challenges than BS and NH dams. As a result of the robust and long-lasting increases in the ability of morphine to induce behavioral sensitization in litter-separated dams, periodic postpartum separation may represent a new animal model of increased vulnerability to substance abuse.

  7. 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.

  8. 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

  9. Involvement of CB1 receptors in the ventral tegmental area in the potentiation of morphine rewarding properties in acquisition but not expression in the conditioned place preference model.

    PubMed

    Rashidy-Pour, Ali; Pahlevani, Pouyan; Vaziri, Anoumid; Shaigani, Pariya; Zarepour, Leila; Vafaei, Abbas Ali; Haghparast, Abbas

    2013-06-15

    The ventral tegmental area (VTA) is a critical part of the brain reward system and has been engaged in mediating rewarding actions. CB1 receptors are one of the receptors that mediate the actions of cannabinoids and endocannabinoids in the central nervous system. Our aim was to determine the potentiating effects of CB1 receptors within the VTA in the acquisition and expression of morphine conditioned place preference (CPP). Stereotaxic surgery was performed bilaterally on each rat to administrate WIN55,212-2 (1, 2 and 4 mmol/0.3 μl DMSO) as CB1 receptor agonist and AM251 (15, 45 and 90 mmol/0.3 μl DMSO) as CB1 receptor antagonist. A three-compartment apparatus was used for the CPP test. The results showed that two doses of WIN55,212-2 (2 and 4 mmol) potentiates the rewarding effects of ineffective dose of morphine (2 mg/kg). We did not see any significant difference between any other doses of WIN55,212-2 and vehicle in the group which received the effective dose of morphine (5mg/kg). Additionally, conditioning scores decreased significantly with the highest administrated dose of AM251 (90 mmol) compared to the vehicle group. We did not observe any significant differences in the experiments for CPP expression by WIN55,212-2 or AM251. It seems that the cannabinoid and opioid systems are in interaction with each other and affect dopaminergic and/or non-dopaminergic neurons in the VTA. Blockade of CB1 receptors may increase GABA release, resulting in the reduction of dopamine output followed by a decrease in the acquisition of morphine-induced CPP in rats.

  10. Reward and learning in the goldfish.

    PubMed

    Lowes, G; Bitterman, M E

    1967-07-28

    An experiment with goldfish showed the effects of change in amount of reward that are predicted from reinforcement theory. The performance of animals shifted from small to large reward improved gradually to the level of unshifted large-reward controls, while the performance of animals shifted from large to small reward remained at the large-reward level. The difference between these results and those obtained in analogous experiments with the rat suggests that reward functions differently in the instrumental learning of the two animals.

  11. Nicotine restores morphine-induced memory deficit through the D1 and D2 dopamine receptor mechanisms in the nucleus accumbens.

    PubMed

    Azizbeigi, Ronak; Ahmadi, Shamseddin; Babapour, Vahab; Rezayof, Ameneh; Zarrindast, Mohammad Reza

    2011-08-01

    Involvement of the dopamine D1 and D2 receptors in the nucleus accumbens (NAc) with interaction between morphine and nicotine on inhibitory avoidance (IA) memory was investigated. A step-through type of inhibitory avoidance tasks was used to assess memory in male Wistar rats. The results showed that subcutaneous (s.c.) administration of morphine (7.5 mg/kg) after training decreased retrieval of IA memory in the animals when tested 24 h later. Pre-test administration of the same dose of morphine significantly reversed the deficiency in retrieval. The results also showed that pre-test administration of nicotine (0.2 and 0.4 mg/kg, s.c.) by itself mimicked the effect of pre-test morphine, and lower doses of nicotine (0.1 and 0.2 mg/kg) also improved the effect of a low dose of morphine (2.5 mg/kg) on retrieval of IA memory. Pre-test intra-NAc administration of the dopamine D1 receptor antagonist, SCH 23390 (0.001 and 0.01 µg/rat), and the dopamine D2 receptor antagonist, sulpiride (0.5 and 1 µg/rat) caused no significant effects on IA memory by themselves, but both prevented reinstatement of the retrieval of IA memory by the effective dose of nicotine (0.4 mg/kg). It can be concluded that the dopaminergic mechanism(s) in the NAc is a crosslink for the effect of morphine and nicotine on reinstatement of retrieval of IA memory impaired by post-training administration of morphine.

  12. 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

  13. Enriched Encoding: Reward Motivation Organizes Cortical Networks for Hippocampal Detection of Unexpected Events

    PubMed Central

    Murty, Vishnu P.; Adcock, R. Alison

    2014-01-01

    Learning how to obtain rewards requires learning about their contexts and likely causes. How do long-term memory mechanisms balance the need to represent potential determinants of reward outcomes with the computational burden of an over-inclusive memory? One solution would be to enhance memory for salient events that occur during reward anticipation, because all such events are potential determinants of reward. We tested whether reward motivation enhances encoding of salient events like expectancy violations. During functional magnetic resonance imaging, participants performed a reaction-time task in which goal-irrelevant expectancy violations were encountered during states of high- or low-reward motivation. Motivation amplified hippocampal activation to and declarative memory for expectancy violations. Connectivity of the ventral tegmental area (VTA) with medial prefrontal, ventrolateral prefrontal, and visual cortices preceded and predicted this increase in hippocampal sensitivity. These findings elucidate a novel mechanism whereby reward motivation can enhance hippocampus-dependent memory: anticipatory VTA-cortical–hippocampal interactions. Further, the findings integrate literatures on dopaminergic neuromodulation of prefrontal function and hippocampus-dependent memory. We conclude that during reward motivation, VTA modulation induces distributed neural changes that amplify hippocampal signals and records of expectancy violations to improve predictions—a potentially unique contribution of the hippocampus to reward learning. PMID:23529005

  14. Enriched encoding: reward motivation organizes cortical networks for hippocampal detection of unexpected events.

    PubMed

    Murty, Vishnu P; Adcock, R Alison

    2014-08-01

    Learning how to obtain rewards requires learning about their contexts and likely causes. How do long-term memory mechanisms balance the need to represent potential determinants of reward outcomes with the computational burden of an over-inclusive memory? One solution would be to enhance memory for salient events that occur during reward anticipation, because all such events are potential determinants of reward. We tested whether reward motivation enhances encoding of salient events like expectancy violations. During functional magnetic resonance imaging, participants performed a reaction-time task in which goal-irrelevant expectancy violations were encountered during states of high- or low-reward motivation. Motivation amplified hippocampal activation to and declarative memory for expectancy violations. Connectivity of the ventral tegmental area (VTA) with medial prefrontal, ventrolateral prefrontal, and visual cortices preceded and predicted this increase in hippocampal sensitivity. These findings elucidate a novel mechanism whereby reward motivation can enhance hippocampus-dependent memory: anticipatory VTA-cortical-hippocampal interactions. Further, the findings integrate literatures on dopaminergic neuromodulation of prefrontal function and hippocampus-dependent memory. We conclude that during reward motivation, VTA modulation induces distributed neural changes that amplify hippocampal signals and records of expectancy violations to improve predictions-a potentially unique contribution of the hippocampus to reward learning.

  15. 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…

  16. 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…

  17. 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.

  18. 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…

  19. Opposing effects of reward and punishment on human vigor.

    PubMed

    Griffiths, Benjamin; Beierholm, Ulrik R

    2017-02-13

    The vigor with which humans and animals engage in a task is often a determinant of the likelihood of the task's success. An influential theoretical model suggests that the speed and rate at which responses are made should depend on the availability of rewards and punishments. While vigor facilitates the gathering of rewards in a bountiful environment, there is an incentive to slow down when punishments are forthcoming so as to decrease the rate of punishments, in conflict with the urge to perform fast to escape punishment. Previous experiments confirmed the former, leaving the latter unanswered. We tested the influence of punishment in an experiment involving economic incentives and contrasted this with reward related behavior on the same task. We found that behavior corresponded with the theoretical model; while instantaneous threat of punishment caused subjects to increase the vigor of their response, subjects' response times would slow as the overall rate of punishment increased. We quantitatively show that this is in direct contrast to increases in vigor in the face of increased overall reward rates. These results highlight the opposed effects of rewards and punishments and provide further evidence for their roles in the variety of types of human decisions.

  20. Opposing effects of reward and punishment on human vigor

    PubMed Central

    Griffiths, Benjamin; Beierholm, Ulrik R.

    2017-01-01

    The vigor with which humans and animals engage in a task is often a determinant of the likelihood of the task’s success. An influential theoretical model suggests that the speed and rate at which responses are made should depend on the availability of rewards and punishments. While vigor facilitates the gathering of rewards in a bountiful environment, there is an incentive to slow down when punishments are forthcoming so as to decrease the rate of punishments, in conflict with the urge to perform fast to escape punishment. Previous experiments confirmed the former, leaving the latter unanswered. We tested the influence of punishment in an experiment involving economic incentives and contrasted this with reward related behavior on the same task. We found that behavior corresponded with the theoretical model; while instantaneous threat of punishment caused subjects to increase the vigor of their response, subjects’ response times would slow as the overall rate of punishment increased. We quantitatively show that this is in direct contrast to increases in vigor in the face of increased overall reward rates. These results highlight the opposed effects of rewards and punishments and provide further evidence for their roles in the variety of types of human decisions. PMID:28205567

  1. Rewarding Good Teachers. A Research Brief.

    ERIC Educational Resources Information Center

    Educational Service District 189, Mt. Vernon, WA.

    According to research of the 1980's in the ERIC system and elsewhere, there seem to be three schools of thought about the most effective ways to reward good teachers and provide incentives for improving teacher performance. The schools of thought described include (1) intrinsic rewards only; (2) specific additional monetary rewards for specific…

  2. Defining rewardable innovation in drug therapy.

    PubMed

    Aronson, Jeffrey K; Ferner, Robin E; Hughes, Dyfrig A

    2012-03-30

    Implementing mechanisms for rewarding those who introduce innovative medicinal products requires a definition of 'rewardable innovation'. Here, we propose a definition of innovation with respect to medicinal products, accompanied by a ranking of the importance of different types of innovativeness, with the aim of providing a basis for rewarding such innovation.

  3. 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

  4. 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.

  5. Reward processing in autism: a thematic series

    PubMed Central

    2012-01-01

    This thematic series presents theoretical and empirical papers focused on understanding autism from the perspective of reward processing deficits. Although the core symptoms of autism have not traditionally been conceptualized with respect to altered reward-based processes, it is clear that brain reward circuitry plays a critical role in guiding social and nonsocial learning and behavior throughout development. Additionally, brain reward circuitry may respond to social sources of information in ways that are similar to responses to primary rewards, and recent clinical data consistently suggest abnormal behavioral and neurobiologic responses to rewards in autism. This thematic series presents empirical data and review papers that highlight the utility of considering autism from the perspective of reward processing deficits. Our hope is that this novel framework may further elucidate autism pathophysiology, with the ultimate goal of yielding novel insights with potential therapeutic implications. PMID:22958239

  6. 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.

  7. Brain Circuits Encoding Reward from Pain Relief

    PubMed Central

    Navratilova, Edita; Atcherley, Christopher; Porreca, Frank

    2015-01-01

    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, activation of midbrain dopamine neurons and release of dopamine in the nucleus accumbens. Understanding of circuits that govern the reward of pain relief may allow the discovery of more effective and satisfying therapies for patients with acute and chronic pain. PMID:26603560

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

    PubMed

    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

  9. Reward system dysfunction in autism spectrum disorders.

    PubMed

    Kohls, Gregor; Schulte-Rüther, Martin; Nehrkorn, Barbara; Müller, Kristin; Fink, Gereon R; Kamp-Becker, Inge; Herpertz-Dahlmann, Beate; Schultz, Robert T; Konrad, Kerstin

    2013-06-01

    Although it has been suggested that social deficits of autism spectrum disorders (ASDs) are related to reward circuitry dysfunction, very little is known about the neural reward mechanisms in ASD. In the current functional magnetic resonance imaging study, we investigated brain activations in response to both social and monetary reward in a group of children with ASD, relative to matched controls. Participants with ASD showed the expected hypoactivation in the mesocorticolimbic circuitry in response to both reward types. In particular, diminished activation in the nucleus accumbens was observed when money, but not when social reward, was at stake, whereas the amygdala and anterior cingulate cortex were hypoactivated within the ASD group in response to both rewards. These data indicate that the reward circuitry is compromised in ASD in social as well as in non-social, i.e. monetary conditions, which likely contributes to atypical motivated behaviour. Taken together, with incentives used in this study sample, there is evidence for a general reward dysfunction in ASD. However, more ecologically valid social reward paradigms are needed to fully understand, whether there is any domain specificity to the reward deficit that appears evident in ASD, which would be most consistent with the ASD social phenotype.

  10. Reward circuitry function in autism spectrum disorders

    PubMed Central

    Felder, Jennifer N.; Green, Steven R.; Rittenberg, Alison M.; Sasson, Noah J.; Bodfish, James W.

    2012-01-01

    Social interaction deficits and restricted repetitive behaviors and interests that characterize autism spectrum disorders (ASDs) may both reflect aberrant functioning of brain reward circuits. However, no neuroimaging study to date has investigated the integrity of reward circuits using an incentive delay paradigm in individuals with ASDs. In the present study, we used functional magnetic resonance imaging to assess blood-oxygen level-dependent activation during reward anticipation and outcomes in 15 participants with an ASD and 16 matched control participants. Brain activation was assessed during anticipation of and in response to monetary incentives and object image incentives previously shown to be visually salient for individuals with ASDs (e.g. trains, electronics). Participants with ASDs showed decreased nucleus accumbens activation during monetary anticipation and outcomes, but not during object anticipation or outcomes. Group × reward-type-interaction tests revealed robust interaction effects in bilateral nucleus accumbens during reward anticipation and in ventromedial prefrontal cortex during reward outcomes, indicating differential responses contingent on reward type in these regions. Results suggest that ASDs are characterized by reward-circuitry hypoactivation in response to monetary incentives but not in response to autism-relevant object images. The clinical implications of the double dissociation of reward type and temporal phase in reward circuitry function in ASD are discussed. PMID:21148176

  11. 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.

  12. Learning Reward Uncertainty in the Basal Ganglia

    PubMed Central

    Bogacz, Rafal

    2016-01-01

    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

  13. 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

  14. 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

  15. Public goods games with reward in finite populations.

    PubMed

    Forsyth, Peter A I; Hauert, Christoph

    2011-07-01

    Public goods games paraphrase the problem of cooperation in game theoretical terms. Cooperators contribute to a public good and thereby increase the welfare of others at a cost to themselves. Defectors consume the public good but do not pay its cost and therefore outperform cooperators. Hence, according to genetic or cultural evolution, defectors should be favored and the public good disappear - despite the fact that groups of cooperators are better off than groups of defectors. The maximization of short term individual profits causes the demise of the common resource to the detriment of all. This outcome can be averted by introducing incentives to cooperate. Negative incentives based on the punishment of defectors efficiently stabilize cooperation once established but cannot initiate cooperation. Here we consider the complementary case of positive incentives created by allowing individuals to reward those that contribute to the public good. The finite-population stochastic dynamics of the public goods game with reward demonstrate that reward initiates cooperation by providing an escape hatch out of states of mutual defection. However, in contrast to punishment, reward is unable to stabilize cooperation but, instead, gives rise to a persistent minority of cooperators.

  16. Stationary Anonymous Sequential Games with Undiscounted Rewards.

    PubMed

    Więcek, Piotr; Altman, Eitan

    Stationary anonymous sequential games with undiscounted rewards are a special class of games that combine features from both population games (infinitely many players) with stochastic games. We extend the theory for these games to the cases of total expected reward as well as to the expected average reward. We show that in the anonymous sequential game equilibria correspond to the limits of those of related finite population games as the number of players grows to infinity. We provide examples to illustrate our results.

  17. Reward, motivation, and reinforcement learning.

    PubMed

    Dayan, Peter; Balleine, Bernard W

    2002-10-10

    There is substantial evidence that dopamine is involved in reward learning and appetitive conditioning. However, the major reinforcement learning-based theoretical models of classical conditioning (crudely, prediction learning) are actually based on rules designed to explain instrumental conditioning (action learning). Extensive anatomical, pharmacological, and psychological data, particularly concerning the impact of motivational manipulations, show that these models are unreasonable. We review the data and consider the involvement of a rich collection of different neural systems in various aspects of these forms of conditioning. Dopamine plays a pivotal, but complicated, role.

  18. Impact of aging on frontostriatal reward processing.

    PubMed

    Vink, Matthijs; Kleerekooper, Iris; van den Wildenberg, Wery P M; Kahn, Rene S

    2015-06-01

    Healthy aging is associated with a progressive decline across a range of cognitive functions. An important factor underlying this decline may be the age-related impairment in stimulus-reward processing. Several studies have investigated age-related effects, but compared young versus old subjects. This is the first study to investigate the effect of aging on brain activation during reward processing within a continuous segment of the adult life span. We scanned 49 healthy adults aged 40-70 years, using functional MRI. We adopted a simple reward task, which allowed separate evaluation of neural responses to reward anticipation and receipt. The effect of reward on performance accuracy and speed was not related to age, indicating that all subjects could perform the task correctly. We identified a whole-brain significant age-related decline of ventral striatum activation during reward anticipation as compared to neutral anticipation. Importantly, the specificity of this finding was underscored by the observation that there was no general decline in activation during anticipation. Activation in the ventral striatum increased with age during reward receipt as compared to receiving neutral outcome. Finally, activation in the ventromedial prefrontal cortex during outcome was not affected by age. Our data demonstrate that the typical shift in striatal activation from reward receipt to reward anticipation in young adults disappears with healthy aging. These changes are consistent the well-ocumented age-related decline of striatal dopamine availability, and may provide a stepping stone for further research of age-related neurodegenerative diseases.

  19. Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

    PubMed

    Smoski, Moria J; Rittenberg, Alison; Dichter, Gabriel S

    2011-12-30

    Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards.

  20. 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.

  1. [Treatment of Cancer Pain and Medical Narcotics].

    PubMed

    Suzuki, Tsutomu

    2015-01-01

    The World Health Organization has reported that when morphine is used to control pain in cancer patients, psychological dependence is not a major concern. Our studies were undertaken to ascertain the modulation of psychological dependence on morphine under a chronic pain-like state in rats. Morphine induced a dose-dependent place preference. We found that inflammatory and neuropathic pain-like states significantly suppressed the morphine-induced rewarding effect. In an inflammatory pain-like state, the suppressive effect was significantly recovered by treatment with a κ-opioid receptor antagonist. In addition, in vivo microdialysis studies clearly showed that the morphine-induced increase in the extracellular levels of dopamine (DA) in the nucleus accumbens (N.Acc.) was significantly decreased in rats 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 may have caused the sustained activation of the κ-opioidergic system within the N.Acc., resulting in suppression of the morphine-induced rewarding effect in rats. On the other hand, we found that attenuation of the morphine-induced place preference under neuropathic pain may result from a decrease in the morphine-induced DA release in the N.Acc with a reduction in the μ-opioid receptor-mediated G-protein activation in the ventral tegmental area (VTA). Moreover, nerve injury results in the continuous release of endogenous β-endorphin to cause the dysfunction of μ-opioid receptors in the VTA. This paper also provides a review to clarify misunderstandings of opioid analgesic use to control pain in cancer patients.

  2. Natural and Drug Rewards Act on Common Neural Plasticity Mechanisms with ΔFosB as a Key Mediator

    PubMed Central

    Pitchers, Kyle K.; Vialou, Vincent; Nestler, Eric J.; Laviolette, Steven R.; Lehman, Michael N.

    2013-01-01

    Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. Recent evidence suggests that natural rewards may cause similar changes in the NAc, suggesting that drugs may activate mechanisms of plasticity shared with natural rewards, and allowing for unique interplay between natural and drug rewards. In this study, we demonstrate that sexual experience in male rats when followed by short or prolonged periods of loss of sex reward causes enhanced amphetamine reward, indicated by sensitized conditioned place preference for low-dose (0.5 mg/kg) amphetamine. Moreover, the onset, but not the longer-term expression, of enhanced amphetamine reward was correlated with a transient increase in dendritic spines in the NAc. Next, a critical role for the transcription factor ΔFosB in sex experience-induced enhanced amphetamine reward and associated increases in dendritic spines on NAc neurons was established using viral vector gene transfer of the dominant-negative binding partner ΔJunD. Moreover, it was demonstrated that sexual experience-induced enhanced drug reward, ΔFosB, and spinogenesis are dependent on mating-induced dopamine D1 receptor activation in the NAc. Pharmacological blockade of D1 receptor, but not D2 receptor, in the NAc during sexual behavior attenuated ΔFosB induction and prevented increased spinogenesis and sensitized amphetamine reward. Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. PMID:23426671

  3. The Risks and Rewards of Sexual Debut

    ERIC Educational Resources Information Center

    Golden, Rachel Lynn; Furman, Wyndol; Collibee, Charlene

    2016-01-01

    The sex-positive framework of sexual development hypothesizes that healthy sexual experiences can be developmentally appropriate and rewarding for adolescents despite the risks involved. Research has not examined whether risky behaviors and rewarding cognitions actually change with sexual debut at a normative or late age. This study measured the…

  4. Status Characteristics, Reward Allocation, and Equity

    ERIC Educational Resources Information Center

    Parcel, Toby L.; Cook, Karen S.

    1977-01-01

    The relationship between a group's power and prestige or status hierarchy and group members' patterns of reward allocation was investigated. The addition of evidence concerning actual task performance results in the alignment of reward and status rankings and encourages the use of distribution rules stressing equity as opposed to equality.…

  5. 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…

  6. 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…

  7. 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.

  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. 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…

  10. 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

  11. 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…

  12. 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.

  13. 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

  14. Effects of Extrinsic Rewards on Intrinsic Motivation in the Classroom.

    ERIC Educational Resources Information Center

    Workman, Edward A.; Williams, Robert L.

    1980-01-01

    Reviews classroom behavior management studies to see if extrinsic rewards affect intrinsic reinforcement value of appropriate classroom behaviors. Conclusion indicates extrinsic rewards are useful. Teachers need not avoid the use of rewards in fear of undermining intrinsic interest. (LAB)

  15. 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.

  16. 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.

  17. A Drosophila model for alcohol reward.

    PubMed

    Kaun, Karla R; Azanchi, Reza; Maung, Zaw; Hirsh, Jay; Heberlein, Ulrike

    2011-05-01

    The rewarding properties of drugs contribute to the development of abuse and addiction. We developed a new assay for investigating the motivational properties of ethanol in the genetically tractable model Drosophila melanogaster. Flies learned to associate cues with ethanol intoxication and, although transiently aversive, the experience led to a long-lasting attraction for the ethanol-paired cue, implying that intoxication is rewarding. Temporally blocking transmission in dopaminergic neurons revealed that flies require activation of these neurons to express, but not develop, conditioned preference for ethanol-associated cues. Moreover, flies acquired, consolidated and retrieved these rewarding memories using distinct sets of neurons in the mushroom body. Finally, mutations in scabrous, encoding a fibrinogen-related peptide that regulates Notch signaling, disrupted the formation of memories for ethanol reward. Our results thus establish that Drosophila can be useful for understanding the molecular, genetic and neural mechanisms underling the rewarding properties of ethanol.

  18. Reward sensitivity and food addiction in women.

    PubMed

    Loxton, Natalie J; Tipman, Renée J

    2016-10-15

    Sensitivity to the rewarding properties of appetitive substances has long been implicated in excessive consumption of palatable foods and drugs of abuse. Previous research focusing on individual differences in reward responsiveness has found heightened trait reward sensitivity to be associated with binge-eating, hazardous drinking, and illicit substance use. Food addiction has been proposed as an extreme form of compulsive-overeating and has been associated with genetic markers of heightened reward responsiveness. However, little research has explicitly examined the association between reward sensitivity and food addiction. Further, the processes by which individual differences in this trait are associated with excessive over-consumption has not been determined. A total of 374 women from the community completed an online questionnaire assessing reward sensitivity, food addiction, emotional, externally-driven, and hedonic eating. High reward sensitivity was significantly associated with greater food addiction symptoms (r = 0.31). Bootstrapped tests of indirect effects found the relationship between reward sensitivity and food addiction symptom count to be uniquely mediated by binge-eating, emotional eating, and hedonic eating (notably, food availability). These indirect effects held even when controlling for BMI, anxiety, depression, and trait impulsivity. This study further supports the argument that high levels of reward sensitivity may offer a trait marker of vulnerability to excessive over-eating, beyond negative affect and impulse-control deficits. That the hedonic properties of food (especially food availability), emotional, and binge-eating behavior act as unique mediators suggest that interventions for reward-sensitive women presenting with food addiction may benefit from targeting food availability in addition to management of negative affect.

  19. Touch massage, a rewarding experience.

    PubMed

    Lindgren, Lenita; Jacobsson, Maritha; Lämås, Kristina

    2014-12-01

    This study aims to describe and analyze healthy individuals' expressed experiences of touch massage (TM). Fifteen healthy participants received whole body touch massage during 60 minutes for two separate occasions. Interviews were analyzed by narrative analysis. Four identifiable storyline was found, Touch massage as an essential need, in this storyline the participants talked about a desire and need for human touch and TM. Another storyline was about, Touch massage as a pleasurable experience and the participants talked about the pleasure of having had TM. In the third storyline Touch massage as a dynamic experience, the informants talked about things that could modulate the experience of receiving TM. In the last storyline, Touch massage influences self-awareness, the participants described how TM affected some of their psychological and physical experiences. Experiences of touch massage was in general described as pleasant sensations and the different storylines could be seen in the light of rewarding experiences.

  20. Intense Sweetness Surpasses Cocaine Reward

    PubMed Central

    Cantin, Lauriane; Ahmed, Serge H.

    2007-01-01

    Background Refined sugars (e.g., sucrose, fructose) were absent in the diet of most people until very recently in human history. Today overconsumption of diets rich in sugars contributes together with other factors to drive the current obesity epidemic. Overconsumption of sugar-dense foods or beverages is initially motivated by the pleasure of sweet taste and is often compared to drug addiction. Though there are many biological commonalities between sweetened diets and drugs of abuse, the addictive potential of the former relative to the latter is currently unknown. Methodology/Principal findings Here we report that when rats were allowed to choose mutually-exclusively between water sweetened with saccharin–an intense calorie-free sweetener–and intravenous cocaine–a highly addictive and harmful substance–the large majority of animals (94%) preferred the sweet taste of saccharin. The preference for saccharin was not attributable to its unnatural ability to induce sweetness without calories because the same preference was also observed with sucrose, a natural sugar. Finally, the preference for saccharin was not surmountable by increasing doses of cocaine and was observed despite either cocaine intoxication, sensitization or intake escalation–the latter being a hallmark of drug addiction. Conclusions Our findings clearly demonstrate that intense sweetness can surpass cocaine reward, even in drug-sensitized and -addicted individuals. We speculate that the addictive potential of intense sweetness results from an inborn hypersensitivity to sweet tastants. In most mammals, including rats and humans, sweet receptors evolved in ancestral environments poor in sugars and are thus not adapted to high concentrations of sweet tastants. The supranormal stimulation of these receptors by sugar-rich diets, such as those now widely available in modern societies, would generate a supranormal reward signal in the brain, with the potential to override self-control mechanisms

  1. 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

  2. Dopamine Modulates Reward-Related Vigor

    PubMed Central

    Beierholm, Ulrik; Guitart-Masip, Marc; Economides, Marcos; Chowdhury, Rumana; Düzel, Emrah; Dolan, Ray; Dayan, Peter

    2013-01-01

    Subjects routinely control the vigor with which they emit motoric responses. However, the bulk of formal treatments of decision-making ignores this dimension of choice. A recent theoretical study suggested that action vigor should be influenced by experienced average reward rate and that this rate is encoded by tonic dopamine in the brain. We previously examined how average reward rate modulates vigor as exemplified by response times and found a measure of agreement with the first suggestion. In the current study, we examined the second suggestion, namely the potential influence of dopamine signaling on vigor. Ninety healthy subjects participated in a double-blind experiment in which they received one of the following: placebo, L-DOPA (which increases dopamine levels in the brain), or citalopram (which has a selective, if complex, effect on serotonin levels). Subjects performed multiple trials of a rewarded odd-ball discrimination task in which we varied the potential reward over time in order to exercise the putative link between vigor and average reward rate. Replicating our previous findings, we found that a significant fraction of the variance in subjects' responses could be explained by our experimentally manipulated changes in average reward rate. Crucially, this relationship was significantly stronger under L-Dopa than under Placebo, suggesting that the impact of average reward levels on action vigor is indeed subject to a dopaminergic influence. PMID:23419875

  3. MODULATION OF FOOD REWARD BY ADIPOSITY SIGNALS

    PubMed Central

    Figlewicz, Dianne P.; Naleid, Amy MacDonald; Sipols, Alfred J.

    2007-01-01

    Extensive historical evidence from the drug abuse literature has provided support for the concept that there is functional communication between central nervous system (CNS) circuitries which subserve reward/motivation, and the regulation of energy homeostasis. This concept is substantiated by recent studies that map anatomical pathways, or which demonstrate that hormones and neurotransmitters associated with energy homeostasis regulation can directly modulate reward and motivation behaviors. Studies from our laboratory have focused specifically on the candidate adiposity hormones, insulin and leptin, and show that these hormones can decrease performance in behavioral paradigms that assess the rewarding or motivating properties of food. Additionally we and others have provided evidence that the ventral tegmental area may be one direct target for these effects, and we are currently exploring other potential anatomical targets. Finally, we are beginning to explore the interaction between adiposity signals, chronic maintenance diet of rats, and different types of food rewards to more closely simulate the current food environments of Westernized societies including the U.S. We propose that future studies of food reward should include a more complex environment in the experimental design that takes into account abundance and variety of rewarding foods, psychological stressors, and choices of reward modalities. PMID:17137609

  4. 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

  5. Reward processing abnormalities in Parkinson's disease.

    PubMed

    Kapogiannis, Dimitrios; Mooshagian, Eric; Campion, Paul; Grafman, Jordan; Zimmermann, Trelawny J; Ladt, Kelsey C; Wassermann, Eric M

    2011-07-01

    The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid-A-mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age-matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk-taking behavior on the Iowa Gambling Task. However, pramipexole increased risk-taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk-taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endophenotype for risk-taking behavior in patients on agonist treatment.

  6. 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

  7. Prosocial Reward Learning in Children and Adolescents

    PubMed Central

    Kwak, Youngbin; Huettel, Scott A.

    2016-01-01

    Adolescence is a period of increased sensitivity to social contexts. To evaluate how social context sensitivity changes over development—and influences reward learning—we investigated how children and adolescents perceive and integrate rewards for oneself and others during a dynamic risky decision-making task. Children and adolescents (N = 75, 8–16 years) performed the Social Gambling Task (SGT, Kwak et al., 2014) and completed a set of questionnaires measuring other-regarding behavior. In the SGT, participants choose amongst four card decks that have different payout structures for oneself and for a charity. We examined patterns of choices, overall decision strategies, and how reward outcomes led to trial-by-trial adjustments in behavior, as estimated using a reinforcement-learning model. Performance of children and adolescents was compared to data from a previously collected sample of adults (N = 102) performing the identical task. We found that that children/adolescents were not only more sensitive to rewards directed to the charity than self but also showed greater prosocial tendencies on independent measures of other-regarding behavior. Children and adolescents also showed less use of a strategy that prioritizes rewards for self at the expense of rewards for others. These results support the conclusion that, compared to adults, children and adolescents show greater sensitivity to outcomes for others when making decisions and learning about potential rewards. PMID:27761125

  8. 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

  9. 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

  10. Endocannabinoid signalling in reward and addiction.

    PubMed

    Parsons, Loren H; Hurd, Yasmin L

    2015-10-01

    Brain endocannabinoid (eCB) signalling influences the motivation for natural rewards (such as palatable food, sexual activity and social interaction) and modulates the rewarding effects of addictive drugs. Pathological forms of natural and drug-induced reward are associated with dysregulated eCB signalling that may derive from pre-existing genetic factors or from prolonged drug exposure. Impaired eCB signalling contributes to dysregulated synaptic plasticity, increased stress responsivity, negative emotional states and cravings that propel addiction. Understanding the contributions of eCB disruptions to behavioural and physiological traits provides insight into the eCB influence on addiction vulnerability.

  11. Endocannabinoid signaling in reward and addiction

    PubMed Central

    Parsons, Loren H.; Hurd, Yasmin L.

    2015-01-01

    Brain endocannabinoid signaling influences the motivation for natural rewards (such as palatable food, sexual activity and social interaction) and modulates the rewarding effects of addictive drugs. Pathological forms of natural and drug-induced reward are associated with dysregulated endocannabinoid signaling that may derive from pre-existing genetic factors or from prolonged drug exposure. Impaired endocannabinoid signaling contributes to dysregulated synaptic plasticity, increased stress responsivity, negative emotional states, and craving that propel addiction. Understanding the contributions of endocannabinoid disruptions to behavioral and physiological traits provides insight into the endocannabinoid influence on addiction vulnerability. PMID:26373473

  12. Dopaminergic Neurons and Brain Reward Pathways

    PubMed Central

    Luo, Sarah X.; Huang, Eric J.

    2017-01-01

    Midbrain dopaminergic (DA) neurons in the substantia nigra pars compacta and ventral tegmental area regulate extrapyramidal movement and important cognitive functions, including motivation, reward associations, and habit learning. Dysfunctions in DA neuron circuitry have been implicated in several neuropsychiatric disorders, including addiction and schizophrenia, whereas selective degeneration of DA neurons in substantia nigra pars compacta is a key neuropathological feature in Parkinson disease. Efforts to understand these disorders have focused on dissecting the underlying causes, as well as developing therapeutic strategies to replenish dopamine deficiency. In particular, the promise of cell replacement therapies for clinical intervention has led to extensive research in the identification of mechanisms involved in DA neuron development. It is hoped that a comprehensive understanding of these mechanisms will lead to therapeutic strategies that improve the efficiency of DA neuron production, engraftment, and function. This review provides a comprehensive discussion on how Wnt/β-catenin and sonic hedgehog–Smoothened signaling mechanisms control the specification and expansion of DA progenitors and the differentiation of DA neurons. We also discuss how mechanisms involving transforming growth factor-β and transcriptional cofactor homeodomain interacting protein kinase 2 regulate the survival and maturation of DA neurons in early postnatal life. These results not only reveal fundamental mechanisms regulating DA neuron development, but also provide important insights to their potential contributions to neuropsychiatric and neurodegenerative diseases. PMID:26724386

  13. Consolidation power of extrinsic rewards: reward cues enhance long-term memory for irrelevant past events.

    PubMed

    Murayama, Kou; Kitagami, Shinji

    2014-02-01

    Recent research suggests that extrinsic rewards promote memory consolidation through dopaminergic modulation processes. However, no conclusive behavioral evidence exists given that the influence of extrinsic reward on attention and motivation during encoding and consolidation processes are inherently confounded. The present study provides behavioral evidence that extrinsic rewards (i.e., monetary incentives) enhance human memory consolidation independently of attention and motivation. Participants saw neutral pictures, followed by a reward or control cue in an unrelated context. Our results (and a direct replication study) demonstrated that the reward cue predicted a retrograde enhancement of memory for the preceding neutral pictures. This retrograde effect was observed only after a delay, not immediately upon testing. An additional experiment showed that emotional arousal or unconscious resource mobilization cannot explain the retrograde enhancement effect. These results provide support for the notion that the dopaminergic memory consolidation effect can result from extrinsic reward.

  14. 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.

  15. Do dopaminergic gene polymorphisms affect mesolimbic reward activation of music listening response? Therapeutic impact on Reward Deficiency Syndrome (RDS).

    PubMed

    Blum, Kenneth; Chen, Thomas J H; Chen, Amanda L H; Madigan, Margaret; Downs, B William; Waite, Roger L; Braverman, Eric R; Kerner, Mallory; Bowirrat, Abdalla; Giordano, John; Henshaw, Harry; Gold, Mark S

    2010-03-01

    affected by an individual's D2 density in the VTA mediated interaction of the NAc. It is therefore hypothesized that carriers of DRD2 A1 allele may respond significantly differently to carriers of the DRD2 A2 genotype. In this regard, carriers of the D2 A1 allele have a blunted response to glucose and monetary rewards. In contrast powerful D2 agonists like bromocryptine show a heightened activation of the reward circuitry only in DRD2 A1 allele carriers. If music causes a powerful activation in spite of the DRD2 A1 allele due to a strong DA neuronal release which subsequently impinges on existing D2 receptors, then it is reasonable to assume that music is a strong indirect D2 agonist (by virtue of DA neuronal release in the NAc) and may have important therapeutic applicability in Reward Deficiency Syndrome (RDS) related behaviors including Substance Use Disorder (SUD). Ross et al. [18] found that music therapy appears to be a novel motivational tool in a severely impaired inpatient sample of patients with co-occurring mental illness and addiction.

  16. 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

  17. Gustatory Reward and the Nucleus Accumbens

    PubMed Central

    Norgren, R.; Hajnal, A.; Mungarndee, S.S.

    2011-01-01

    The concept of reward is central to psychology, but remains a cipher for neuroscience. Considerable evidence implicates dopamine in the process of reward and much of the data derives from the nucleus accumbens. Gustatory stimuli are widely used for animal studies of reward, but the connections between the taste and reward systems are unknown. In a series of experiments, our laboratory has addressed this issue using functional neurochemistry and neuroanatomy. First, using microdialysis probes, we demonstrated that sapid sucrose releases dopamine in the nucleus accumbens. The effect is dependent on oral stimulation and concentration. We subsequently determined that this response was independent of the thalamocortical gustatory system, but substantially blunted by damage to the parabrachial limbic taste projection. Further experiments using c-fos histochemistry confirmed that the limbic pathway was the prime carrier for the gustatory afferent activity that drives accumbens dopamine release. PMID:16822531

  18. Brain Reward Circuits in Morphine Addiction

    PubMed Central

    Kim, Juhwan; Ham, Suji; Hong, Heeok; Moon, Changjong; Im, Heh-In

    2016-01-01

    Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate’s innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences. PMID:27506251

  19. Neural representations of subjective reward value.

    PubMed

    Peters, J; Büchel, C

    2010-12-01

    Decision neuroscience suggests that there exists a core network for the subjective valuation of rewards from a range of different domains, encompassing the ventral striatum and regions of the orbitofrontal cortex (OFC), in particular the ventromedial aspect of the OFC. Here we first review ways to measure subjective value experimentally in a cognitive neuroscience context, and provide a brief overview over different types of value (outcome, goal and decision value). We then compare results of functional neuroimaging studies of subjective value representations across these different types of value. Our analysis suggests that the same region of the mOFC represents the outcome values of primary reinforcers, but also more complex decision values in which multiple dimensions of the reward need to be integrated. The subjective (hedonic) experience of processing highly valued decision options (regardless of whether they refer to actually experienced rewards or merely potential future rewards) appears to be what is reflected in value-related mOFC activity.

  20. 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

  1. 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.

  2. Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning.

    PubMed

    Kim, Sang Hee; Yoon, HeungSik; Kim, Hackjin; Hamann, Stephan

    2015-09-01

    In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment.

  3. 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.

  4. Interrelated mechanisms in reward and learning.

    PubMed

    Lajtha, Abel

    2008-01-01

    This brief review is focused on recent work in our laboratory, in which we assayed nicotine-induced neurotransmitter changes, comparing it to changes induced by other compounds and examined the receptor systems and their interactions that mediate the changes. The primary aim of our studies is to examine the role of neurotransmitter changes in reward and learning processes. We find that these processes are interlinked and interact in that reward-addiction mechanisms include processes of learning and learning-memory mechanisms include processes of reward. In spite being interlinked, the two processes have different functions and distinct properties and our long-term aim is to identify factors that control these processes and the differences among the processes. Here, we discuss reward processes, which we define as changes examined after administration of nicotine, cocaine or food, each of which induces changes in neurotransmitter levels and functions in cognitive areas as well as in reward areas. The changes are regionally heterogeneous and are drug or stimulus specific. They include changes in the transmitters assayed (catecholamines, amino acids, and acetylcholine) and also in their metabolites, hence, in addition to release, uptake and metabolism are involved. Many receptors modulate the response with direct and indirect effects. The involvement of many transmitters, receptors and their interactions and the stimulus specificity of the response indicated that each function, reward and learning represents the involvement of different pattern of changes with a different stimulus, therefore, many different learning and many different reward processes are active, which allow stimulus specific responses. The complex pattern of reward-induced changes in neurotransmitters is only a part of the multiple changes observed, but one which has a crucial and controlling function.

  5. The circadian clock, reward, and memory.

    PubMed

    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.

  6. Ghrelin at the interface of obesity and reward.

    PubMed

    Schellekens, Harriët; Dinan, Timothy G; Cryan, John F

    2013-01-01

    The prevalence of obesity continues to increase and has reached epidemic proportions. Accumulating data over the past few decades have given us key insights and broadened our understanding of the peripheral and central regulation of energy homeostasis. Despite this, the currently available pharmacological treatments, reducing body weight, remain limited due to poor efficacy and side effects. The gastric peptide ghrelin has been identified as the only orexigenic hormone from the periphery to act in the hypothalamus to stimulate food intake. Recently, a role for ghrelin and its receptor at the interface between homeostatic control of appetite and reward circuitries modulating the hedonic aspects of food has also emerged. Nonhomeostatic factors such as the rewarding and motivational value of food, which increase with food palatability and caloric content, can override homeostatic control of food intake. This nonhomeostatic decision to eat leads to overconsumption beyond nutritional needs and is being recognized as a key component in the underlying causes for the increase in obesity incidence worldwide. In addition, the hedonic feeding behavior has been linked to food addiction and an important role for ghrelin in the development of addiction has been suggested. Moreover, plasma ghrelin levels are responsive to conditions of stress, and recent evidence has implicated ghrelin in stress-induced food-reward behavior. The prominent role of the ghrelinergic system in the regulation of feeding gives rise to it as an effective target for the development of successful antiobesity pharmacotherapies that not only affect satiety but also selectively modulate the rewarding properties of food and reduce the desire to eat.

  7. 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.

  8. The endocannabinoid system and nondrug rewarding behaviours.

    PubMed

    Fattore, Liana; Melis, Miriam; Fadda, Paola; Pistis, Marco; Fratta, Walter

    2010-07-01

    Rewarding behaviours such as sexual activity, eating, nursing, parenting, social interactions, and play activity are conserved strongly in evolution, and they are essential for development and survival. All of these behaviours are enjoyable and represent pleasant experiences with a high reward value. Remarkably, rewarding behaviours activate the same brain circuits that mediate the positive reinforcing effects of drugs of abuse and of other forms of addiction, such as gambling and food addiction. Given the involvement of the endocannabinoid system in a variety of physiological functions of the nervous system, it is not surprising that it takes part in the complex machinery that regulates gratification and perception of pleasure. In this review, we focus first on the role of the endocannabinoid system in the modulation of neural activity and synaptic functions in brain regions that are involved in natural and nonnatural rewards (namely, the ventral tegmental area, striatum, amygdala, and prefrontal cortex). Then, we examine the role of the endocannabinoid system in modulating behaviours that directly or indirectly activate these brain reward pathways. More specifically, current knowledge of the effects of the pharmacological manipulation of the endocannabinoid system on natural (eating, sexual behaviour, parenting, and social play) and pathological (gambling) rewarding behaviours is summarised and discussed.

  9. Brain Structural Substrates of Reward Dependence during Behavioral Performance

    PubMed Central

    Hamann, Janne M.; Averbeck, Bruno B.

    2014-01-01

    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

  10. 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

  11. 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

    2016-04-05

    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.

  12. Role of D1/D2 dopamine receptors in the CA1 region of the rat hippocampus in the rewarding effects of morphine administered into the ventral tegmental area.

    PubMed

    Esmaeili, Mohammad-Hossein; Kermani, Mojtaba; Parvishan, Asghar; Haghparast, Abbas

    2012-05-16

    Considerable evidences show that the VTA, as a major source of dopamine neurons projecting to cortical and limbic regions, has a major role in cognitive and motivating aspects of addiction. The current study assessed the ability of the selective D1 receptor antagonist SCH 23390 and D2 receptor antagonist sulpiride administrated into the CA1 region of hippocampus (dorsal hippocampus) to alter the rewarding effects of intra-VTA administration of morphine using the conditioned place preference (CPP). After bilaterally implantation of cannulae into the CA1 and/or VTA in adult male Wistar rats weighing 210-310 g, dose-response effects of different doses of intra-VTA morphine (0.03, 0.1, 0.3, 1 and 3 μg/side) on CPP paradigm were evaluated and animal displacement, conditioning score and locomotor activity were recorded by Ethovision software. In the next experiments, SCH 23390 (0.02, 0.05, 0.2 and 0.5 μg/side) or sulpiride (0.25, 0.75, 1.5 and 3 μg/side) were injected into the CA1, 5 min after intra-VTA injection of morphine during 3 days conditioning phase. Our results showed that intra-VTA morphine dose-dependently induces CPP in rats. Moreover, the blocking D1 and D2 receptors in the dorsal hippocampus decreased intra-VTA morphine-induced CPP significantly (P<0.01). Intra-CA1 administration of these antagonists alone, in all doses, could not induce CPP. We suggest that D1 and D2 receptors in the CA1 region of hippocampus have a key role in the development of CPP induced by morphine at the level of the VTA. It seems that there is an interaction between dopaminergic and opioidergic systems in these areas in reward circuit.

  13. Neurons in monkey dorsal raphe nucleus code beginning and progress of step-by-step schedule, reward expectation, and amount of reward outcome in the reward schedule task.

    PubMed

    Inaba, Kiyonori; Mizuhiki, Takashi; Setogawa, Tsuyoshi; Toda, Koji; Richmond, Barry J; Shidara, Munetaka

    2013-02-20

    The dorsal raphe nucleus is the major source of serotonin in the brain. It is connected to brain regions related to reward processing, and the neurons show activity related to predicted reward outcome. Clinical observations also suggest that it is important in maintaining alertness and its apparent role in addiction seems to be related to reward processing. Here, we examined whether the neurons in dorsal raphe carry signals about reward outcome and task progress during multitrial schedules. We recorded from 98 single neurons in dorsal raphe of two monkeys. The monkeys perform one, two, or three visual discrimination trials (schedule), obtaining one, two, or three drops of liquid. In the valid cue condition, the length and brightness of a visual cue indicated schedule progress and reward amount, respectively. In the random cue condition, the visual cue was randomly presented with respect to schedule length and reward amount. We found information encoded about (1) schedule onset, (2) reward expectation, (3) reward outcome, and (4) reward amount in the mean firing rates. Information theoretic analysis showed that the temporal variation of the neuronal responses contained additional information related to the progress of the schedule toward the reward rather than only discriminating schedule onset or reward/no reward. When considered in light of all that is known about the raphe in anatomy, physiology, and behavior, the rich encoding about both task progress and predicted reward outcome makes the raphe a strong candidate for providing signals throughout the brain to coordinate persistent goal-seeking behavior.

  14. Paraventricular Thalamus Balances Danger and Reward.

    PubMed

    Choi, Eun A; McNally, Gavan P

    2017-03-15

    Foraging animals balance the need to seek food and energy against the accompanying dangers of injury and predation. To do so, they rely on learning systems encoding reward and danger. Whereas much is known about these separate learning systems, little is known about how they interact to shape and guide behavior. Here we show a key role for the rat paraventricular nucleus of the thalamus (PVT), a nucleus of the dorsal midline thalamus, in this interaction. First, we show behavioral competition between reward and danger: the opportunity to seek food reward negatively modulates expression of species-typical defensive behavior. Then, using a chemogenetic approach expressing the inhibitory hM4Di designer receptor exclusively activated by a designer drug in PVT neurons, we show that the PVT is central to this behavioral competition. Chemogenetic PVT silencing biases behavior toward either defense or reward depending on the experimental conditions, but does not consistently favor expression of one over the other. This bias could not be attributed to changes in fear memory retrieval, learned safety, or memory interference. Rather, our results demonstrate that the PVT is essential for balancing conflicting behavioral tendencies toward danger and reward, enabling adaptive responding under this basic selection pressure.SIGNIFICANCE STATEMENT Among the most basic survival problems faced by animals is balancing the need to seek food and energy against the accompanying dangers of injury and predation. Although much is known about the brain mechanisms that underpin learning about reward and danger, little is known about how these interact to solve basic survival problems. Here we show competition between defensive (to avoid predatory detection) and approach (to obtain food) behavior. We show that the paraventricular thalamus, a nucleus of the dorsal midline thalamus, is integral to this behavioral competition. The paraventricular thalamus balances the competing behavioral demands

  15. Electrodermal Response to Reward and Non-Reward Among Children With Autism.

    PubMed

    Neuhaus, Emily; Bernier, Raphael A; Beauchaine, Theodore P

    2015-08-01

    Pervasive social difficulties among individuals with autism spectrum disorder (ASD) are often construed as deriving from reduced sensitivity to social stimuli. Behavioral and neurobiological evidence suggests that typical individuals show preferential processing of social (e.g., voices, faces) over nonsocial (e.g., nonvocal sounds, images of objects) information, whereas individuals with ASD may not. This reduction in sensitivity may reflect disrupted reward processing [Dawson & Bernier, ], with significant developmental consequences for affected individuals. In this study, we explore effects of social and monetary reward on behavioral and electrodermal responses (EDRs) among 8- to 12-year-old boys with (n = 18) and without (n = 18) ASD, with attention to the potential moderating effects of stimulus familiarity. During a simple matching task, participants with and without ASD had marginally slower reactions during social vs. nonsocial reward, and boys with ASD had less accurate responses than controls. Compared to baseline, reward and non-reward conditions elicited more frequent and larger EDRs for participants as a whole, and both groups showed similar patterns of EDR change within reward blocks. However, boys with and without ASD differed in their EDRs to non-reward, and response amplitude was correlated with social and emotional functioning. These findings provide some support for altered reward responding in ASD at the autonomic level, and highlight the discontinuation of reward as an important component of reward-based learning that may play a role in shaping behavior and guiding specialized brain development to subserve social behavior and cognition across the lifespan.

  16. 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

  17. Suppression of Dopamine Neurons Mediates Reward

    PubMed Central

    Yamagata, Nobuhiro; Abe, Ayako; Tanimoto, Hiromu

    2016-01-01

    Massive activation of dopamine neurons is critical for natural reward and drug abuse. In contrast, the significance of their spontaneous activity remains elusive. In Drosophila melanogaster, depolarization of the protocerebral anterior medial (PAM) cluster dopamine neurons en masse signals reward to the mushroom body (MB) and drives appetitive memory. Focusing on the functional heterogeneity of PAM cluster neurons, we identified that a single class of PAM neurons, PAM-γ3, mediates sugar reward by suppressing their own activity. PAM-γ3 is selectively required for appetitive olfactory learning, while activation of these neurons in turn induces aversive memory. Ongoing activity of PAM-γ3 gets suppressed upon sugar ingestion. Strikingly, transient inactivation of basal PAM-γ3 activity can substitute for reward and induces appetitive memory. Furthermore, we identified the satiety-signaling neuropeptide Allatostatin A (AstA) as a key mediator that conveys inhibitory input onto PAM-γ3. Our results suggest the significance of basal dopamine release in reward signaling and reveal a circuit mechanism for negative regulation. PMID:27997541

  18. Reward Contexts Extend Dopamine Signals to Unrewarded Stimuli

    PubMed Central

    Kobayashi, Shunsuke; Schultz, Wolfram

    2014-01-01

    Summary Basic tenets of sensory processing emphasize the importance of accurate identification and discrimination of environmental objects [1]. Although this principle holds also for reward, the crucial acquisition of reward for survival would be aided by the capacity to detect objects whose rewarding properties may not be immediately apparent. Animal learning theory conceptualizes how unrewarded stimuli induce behavioral reactions in rewarded contexts due to pseudoconditioning and higher-order context conditioning [2–6]. We hypothesized that the underlying mechanisms may involve context-sensitive reward neurons. We studied short-latency activations of dopamine neurons to unrewarded, physically salient stimuli while systematically changing reward context. Dopamine neurons showed substantial activations to unrewarded stimuli and their conditioned stimuli in highly rewarded contexts. The activations decreased and often disappeared entirely with stepwise separation from rewarded contexts. The influence of reward context suggests that dopamine neurons respond to real and potential reward. The influence of reward context is compatible with the reward nature of phasic dopamine responses. The responses may facilitate rapid, default initiation of behavioral reactions in environments usually containing reward. Agents would encounter more and miss less reward, resulting in survival advantage and enhanced evolutionary fitness. PMID:24332545

  19. 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

  20. Food after deprivation rewards the earlier eating.

    PubMed

    Booth, David A; Jarvandi, Soghra; Thibault, Louise

    2012-12-01

    Food intake can be increased by learning to anticipate the omission of subsequent meals. We present here a new theory that such anticipatory eating depends on an associative process of instrumental reinforcement by the nutritional repletion that occurs when access to food is restored. Our evidence over the last decade from a smooth-brained omnivore has been that food after deprivation rewards intake even when those reinforced ingestive responses occur long before the physiological signals from renewed assimilation. Effects of food consumed after self-deprivation might therefore reward extra eating in human beings, through brain mechanisms that could operate outside awareness. That would have implications for efforts to reduce body weight. This food reward mechanism could be contributing to the failure of the dietary component of interventions on obesity within controlled trials of the management or prevention of disorders such as hypertension, atherosclerosis and type 2 diabetes.

  1. 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

  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. 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

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

    PubMed

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

    2011-03-01

    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.

  5. Endocannabinoid signaling system and brain reward: emphasis on dopamine.

    PubMed

    Gardner, Eliot L

    2005-06-01

    The brain's reward circuitry consists of an "in series" circuit of dopaminergic (DA) neurons in the ventral tegmental area (VTA), nucleus accumbens (Acb), and that portion of the medial forebrain bundle (MFB) which links the VTA and Acb. Drugs which enhance brain reward (and have derivative addictive potential) have common actions on this core DA reward system and on animal behaviors relating to its function. Such drugs enhance electrical brain-stimulation reward in this reward system; enhance neural firing and DA tone within it; produce conditioned place preference (CPP), a behavioral model of incentive motivation; are self-administered; and trigger reinstatement of drug-seeking behavior in animals extinguished from drug self-administration. Cannabinoids were long considered different from other reward-enhancing drugs in reward efficacy and in underlying neurobiological substrates activated. However, it is now clear that cannabinoids activate these brain reward processes and reward-related behaviors in similar fashion to other reward-enhancing drugs. This brief review discusses the roles that endogenous cannabinoids (especially activation of the CB1 receptor) may play within the core reward system, and concludes that while cannabinoids activate the reward pathways in a manner consistent with other reward-enhancing drugs, the neural mechanisms by which this occurs may differ.

  6. Incentive sensitization by previous amphetamine exposure: increased cue-triggered "wanting" for sucrose reward.

    PubMed

    Wyvell, C L; Berridge, K C

    2001-10-01

    We reported previously that an amphetamine microinjection into the nucleus accumbens enables Pavlovian reward cues in a conditioned incentive paradigm to trigger excessive instrumental pursuit. Here we show that sensitization caused by previous amphetamine administration also causes reward cues to trigger excessive pursuit of their associated reward, even when sensitized rats are tested in a drug-free state. Rats learned to lever press for sucrose pellets, and they separately learned to associate sucrose pellets with Pavlovian cues (30 sec auditory cues). Amphetamine sensitization was induced by six daily injections of amphetamine (3 mg/kg, i.p.; controls received saline). Rats were tested for lever pressing under extinction conditions 10 d later, after a bilateral microinjection of intra-accumbens vehicle or amphetamine (5 microg/0.5 microl per side). Cue-triggered pursuit of sucrose reward was assessed by increases in pressing on the sucrose-associated lever during intermittent presentations of a free conditioned stimulus (CS+) sucrose cue. Sensitized rats pressed at normal levels during baseline and during the CS-, but the CS+ triggered 100% greater increases in pressing from sensitized rats than from control rats after vehicle microinjection. Sensitization therefore enhanced the incentive salience attributed to the CS+ even when rats were tested while drug-free. For control rats, a microinjection of intra-accumbens amphetamine was needed to produce the same enhancement of cue-triggered reward "wanting." The amphetamine microinjection also interacted synergistically in sensitized rats to produce intrusive cue-triggered pursuit behaviors (e.g., investigatory sniffing) that interfered with goal-directed lever pressing. These results support the incentive-sensitization theory postulate that sensitization causes excessive cue-triggered "wanting" for an associated reward.

  7. Effects of striatal lesions on components of choice: Reward discrimination, preference, and relative valuation.

    PubMed

    Ricker, Joshua M; Kopchock, Richard J; Drown, Rachel M; Cromwell, Howard C

    2016-12-15

    The striatum is a key structure involved in reward processing and choice. Recently, we have developed a paradigm to explore how components of reward processing work together or independently during choice behavior. These components include reward discrimination, preference and relative valuation, and the goal of the present study was to determine how the striatum is involved in these dissociable components during this novel free choice paradigm. We tested choice utilizing two different outcome series with one being a more straightforward single-option discrimination anchored by a 0 reward outcome, and the other as a multi-option outcome discrimination of greater difficulty. We compared the free choice reward task to a sequential reward task and an extinction task. Striatal lesions impaired responding only in the free choice version with alterations in both appetitive and consummatory measures. Ventral striatal lesions had greater impact altering discrimination, preference and relative valuation in both the single and multi-option week studies. A major factor involved in these deficits was a significant aversion to the multi-option that contained a larger outcome option but with a longer delay to reward. Dorsal striatal lesions caused less impairment even leading to enhanced choice behavior compared to control animals during the more difficult multi-option free choice series. Overall, the results suggest that the context of action is crucial when linking striatal function to choice behavior and its diverse components. The implications include the idea that striatal involvement in decision-making is increased when responses are self-paced and diverse in a more naturalistic environment.

  8. Long-lasting sensitization of reward-directed behavior by amphetamine.

    PubMed

    Mendez, Ian A; Williams, Matthew T; Bhavsar, Atasi; Lu, Annie P; Bizon, Jennifer L; Setlow, Barry

    2009-07-19

    Exposure to psychostimulant drugs of abuse such as amphetamine can result in long-lasting "sensitization" of reward-directed behavior, such that subjects display enhancements in behavior directed by and toward rewards and reward-predictive cues (i.e. "incentive sensitization"). The purpose of these experiments was to determine the degree to which such sensitization resulting from chronic amphetamine exposure influences both appetitive and consummatory food-motivated behavior. Adult male Long-Evans rats received daily i.p. injections of D-amphetamine (2.0 mg/kg) or saline vehicle for five consecutive days. This amphetamine exposure regimen produced lasting sensitization to the acute locomotor stimulant effect of the drug. One month after drug exposure rats were tested for instrumental responding (lever pressing) for food reward under various response schedules. Two months after drug exposure, rats were tested for food consumption in a discriminative Pavlovian context-potentiated eating task, involving pairings of one context with food and another context with no food. Amphetamine exposed rats showed significantly greater instrumental responding for food reward than saline controls, particularly under conditions of high response ratios. In the potentiated eating task, testing under conditions of food satiation revealed that amphetamine exposed rats ate significantly more than saline controls in the food-paired context. These experiments demonstrate that amphetamine exposure can cause enduring increases in both appetitive and consummatory aspects of natural reward-directed behavior. Such long-lasting incentive sensitization could account in part for the propensity for relapse in drug addiction, as well as for reported enhancements in non-drug reward-related behavior.

  9. Shift of circadian feeding pattern by high-fat diets is coincident with reward deficits in obese mice.

    PubMed

    Morales, Lidia; Del Olmo, Nuria; 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.

  10. Reward: From Basic Reinforcers to Anticipation of Social Cues.

    PubMed

    Rademacher, Lena; Schulte-Rüther, Martin; Hanewald, Bernd; Lammertz, Sarah

    2017-01-01

    Reward processing plays a major role in goal-directed behavior and motivation. On the neural level, it is mediated by a complex network of brain structures called the dopaminergic reward system. In the last decade, neuroscientific researchers have become increasingly interested in aspects of social interaction that are experienced as rewarding. Recent neuroimaging studies have provided evidence that the reward system mediates the processing of social stimuli in a manner analogous to nonsocial rewards and thus motivates social behavior. In this context, the neuropeptide oxytocin is assumed to play a key role by activating dopaminergic reward pathways in response to social cues, inducing the rewarding quality of social interactions. Alterations in the dopaminergic reward system have been found in several psychiatric disorders that are accompanied by social interaction and motivation problems, for example autism, attention deficit/hyperactivity disorder, addiction disorders, and schizophrenia.

  11. Rewarded outcomes enhance reactivation of experience in the hippocampus.

    PubMed

    Singer, Annabelle C; Frank, Loren M

    2009-12-24

    Remembering experiences that lead to reward is essential for survival. The hippocampus is required for forming and storing memories of events and places, but the mechanisms that associate specific experiences with rewarding outcomes are not understood. Event memory storage is thought to depend on the reactivation of previous experiences during hippocampal sharp wave ripples (SWRs). We used a sequence switching task that allowed us to examine the interaction between SWRs and reward. We compared SWR activity after animals traversed spatial trajectories and either received or did not receive a reward. Here, we show that rat hippocampal CA3 principal cells are significantly more active during SWRs following receipt of reward. This SWR activity was further enhanced during learning and reactivated coherent elements of the paths associated with the reward location. This enhanced reactivation in response to reward could be a mechanism to bind rewarding outcomes to the experiences that precede them.

  12. Identifying nurses' rewards: a qualitative categorization study in Belgium

    PubMed Central

    De Gieter, Sara; De Cooman, Rein; Pepermans, Roland; Caers, Ralf; Du Bois, Cindy; Jegers, Marc

    2006-01-01

    Background Rewards are important in attracting, motivating and retaining the most qualified employees, and nurses are no exception to this rule. This makes the establishment of an efficient reward system for nurses a true challenge for every hospital manager. A reward does not necessarily have a financial connotation: non-financial rewards may matter too, or may even be more important. Therefore, the present study examines nurses' reward perceptions, in order to identify potential reward options. Methods To answer the research question "What do nurses consider a reward and how can these rewards be categorized?", 20 in-depth semi-structured interviews with nurses were conducted and analysed using discourse and content analyses. In addition, the respondents received a list of 34 rewards (derived from the literature) and were asked to indicate the extent to which they perceived each of them to be rewarding. Results Discourse analysis revealed three major reward categories: financial, non-financial and psychological, each containing different subcategories. In general, nurses more often mentioned financial rewards spontaneously in the interview, compared to non-financial and psychological rewards. The questionnaire results did not, however, indicate a significant difference in the rewarding potential of these three categories. Both the qualitative and quantitative data revealed that a number of psychological and non-financial rewards were important for nurses in addition to their monthly pay and other remunerations. In particular, appreciation for their work by others, compliments from others, presents from others and contact with patients were highly valued. Moreover, some demographical variables influenced the reward perceptions. Younger and less experienced nurses considered promotion possibilities as more rewarding than the older and more senior ones. The latter valued job security and working for a hospital with a good reputation higher than their younger and more

  13. Associations between sleep parameters and food reward.

    PubMed

    McNeil, Jessica; Cadieux, Sébastien; Finlayson, Graham; Blundell, John E; Doucet, Éric

    2015-06-01

    This study examined the effects of acute, isocaloric aerobic and resistance exercise on different sleep parameters, and whether changes in these sleep parameters between sessions were related to next morning food reward. Fourteen men and women (age: 21.9 ± 2.7 years; body mass index: 22.7 ± 1.9 kg m(-) ²) participated in three randomized crossover sessions: aerobic exercise; resistance exercise; and sedentary control. Target exercise energy expenditure was matched at 4 kcal kg(-1) of body weight, and performed at 70% of VO2peak or 70% of 1 repetition-maximal. Sleep was measured (accelerometry) for 22 h following each session. The 'wanting' for visual food cues (validated computer task) was assessed the next morning. There were no differences in sleep parameters and food 'wanting' between conditions. Decreases in sleep duration and earlier wake-times were significantly associated with increased food 'wanting' between sessions (P = 0.001). However, these associations were no longer significant after controlling for elapsed time between wake-time and the food reward task. These findings suggest that shorter sleep durations and earlier wake-times are associated with increased food reward, but these associations are driven by elapsed time between awakening and completion of the food reward task.

  14. Lowered Expectations: How Schools Reward Incompetence.

    ERIC Educational Resources Information Center

    Jackson, Bruce

    1985-01-01

    Playing "dumb" can earn students easier classes, lower expectations, reduced pressure, and individual attention. Schools can stop rewarding failure by making remedial classes difficult, backing up homework policies with unappealing alternatives, providing penalties for attendance violations, and deglamorizing alternatives to regular programs. (PGD)

  15. 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.

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. Model of Educational Rewards for Innovative Teaching.

    ERIC Educational Resources Information Center

    Monroe County Intermediate School District, MI.

    The purpose of this project is to encourage innovative teaching through support and reward systems; specifically, its objectives are the generation, implementation, and sharing of innovative curricular ideas and classroom procedures. Participants are teachers, students, parents, other school staff and the community. The following elements are…

  1. EFFECT OF EXTRINSIC REWARDS ON MOTIVATION.

    ERIC Educational Resources Information Center

    GLADSTONE, ROY

    THE SPECIFIC PROBLEM WAS WHETHER HUMANS, AFTER HAVING BEEN TRAINED ON A GIVEN REWARD SCHEDULE TO ACT IN A GIVEN WAY IN GIVEN CIRCUMSTANCES, WILL EXHIBIT FIXED EXTINCTION BEHAVIOR REGARDLESS OF THE DIFFERENCES BETWEEN THE TRAINING AND THE EXTINCTION PERIODS. SUBJECTS WERE 360 COLLEGE STUDENTS WHO HAD VOLUNTEERED FOR THE EXPERIMENT. AN APPARATUS WAS…

  2. Alterations of reward mechanisms in bulbectomised rats.

    PubMed

    Grecksch, Gisela; Becker, Axel

    2015-06-01

    The positive association between alcoholism and depression is a common clinical observation. We investigated the relationship between depression and reward mechanisms using a validated animal model for depressive-like behaviour, the olfactory bulbectomy in rats. The effects of bilateral olfactory bulbectomy on reward mechanisms were studied in two different experimental paradigms - the voluntary self-administration of ethanol and the conditioned place preference to alcohol injection and compared to the effects of ethanol on locomotor activity and body core temperature. The voluntary ethanol intake was increased significantly in bulbectomised rats in a drinking experiment and also after a period of abstinence. Conditioned place preference (CPP) was induced in all animals. However, bulbectomised rats needed a higher dose of alcohol to produce CPP. The sedative effect of ethanol on locomotor activity was reduced in bulbectomised animals. Measurement of body temperature revealed a dose-dependent hypothermic effect of ethanol in both groups. These results suggest that the reward mechanisms may be altered in this animal model as a common phenomenon associated with depression. Furthermore, they support the hypothesis that the addictive and/or rewarding properties of some drugs of abuse may be modified in depression.

  3. 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.

  4. Reward Motivation Accelerates the Onset of Neural Novelty Signals in Humans to 85 Milliseconds

    PubMed Central

    Bunzeck, Nico; Doeller, Christian F.; Fuentemilla, Lluis; Dolan, Raymond J.; Duzel, Emrah

    2009-01-01

    Summary The neural responses that distinguish novel from familiar items in recognition memory tasks are remarkably fast in both humans and nonhuman primates. In humans, the earliest onsets of neural novelty effects emerge at about ∼150–200 ms after stimulus onset [1–5]. However, in recognition memory studies with nonhuman primates, novelty effects can arise at as early as 70–80 ms [6, 7]. Here, we address the possibility that this large species difference in onset latencies is caused experimentally by the necessity of using reward reinforcement to motivate the detection of novel or familiar items in nonhuman primates but not in humans. Via magnetoencephalography in humans, we show in two experiments that the onset of neural novelty signals is accelerated from ∼200 ms to ∼85 ms if correct recognition memory for either novel or familiar items is rewarded. Importantly, this acceleration is independent of whether the detection of the novel or the familiar scenes is rewarded. Furthermore, this early novelty effect contributed to memory retrieval because neural reward responses, which were contingent upon novelty detection, followed ∼100 ms later. Thus, under the contextual influence of reward motivation, behaviorally relevant novelty signals emerge much faster than previously held possible in humans. PMID:19576774

  5. Dissecting components of reward: 'liking', 'wanting', and learning.

    PubMed

    Berridge, Kent C; Robinson, Terry E; Aldridge, J Wayne

    2009-02-01

    In recent years significant progress has been made delineating the psychological components of reward and their underlying neural mechanisms. Here we briefly highlight findings on three dissociable psychological components of reward: 'liking' (hedonic impact), 'wanting' (incentive salience), and learning (predictive associations and cognitions). A better understanding of the components of reward, and their neurobiological substrates, may help in devising improved treatments for disorders of mood and motivation, ranging from depression to eating disorders, drug addiction, and related compulsive pursuits of rewards.

  6. 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

  7. Obesity and the neurocognitive basis of food reward and the control of intake.

    PubMed

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

    2015-07-01

    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.

  8. Brain mechanisms of drug reward and euphoria.

    PubMed

    Wise, R A; Bozarth, M A

    1985-01-01

    Drugs of abuse have in common the fact that they serve as biological rewards. They presumably do so because of their ability to activate endogenous brain circuitry. By determining the brain circuitry activated by rewarding drug injections, much can be learned about the degree to which there is a common basis for the abuse liability of seemingly different drugs. The brain circuitry activated by two classes of abused drugs, psychomotor stimulants and opiates, is now partially understood; the current evidence suggests a shared mechanism of stimulant reward and opiate reward. The identified portion of the circuitry involves dopamine-containing cells of the ventral tegmental area and their fiber projections to the cells of the nucleus accumbens. Morphine activates these cells in the region of the cell bodies; it may have direct actions on receptors imbedded in the dopaminergic cell membrane, or it may act on afferent terminals that synapse on the dopaminergic cell bodies or dendrites. Cocaine and amphetamine act at the terminals of the dopaminergic fibers to nucleus accumbens and perhaps other structures. The shared activation of the dopaminergic input to nucleus accumbens accounts for the behaviorally activating and the rewarding effects of both stimulants and opiates (the opiate stimulant action is not widely known because it is usually masked by depressant actions of opiates in other, antagonistic, brain circuits). The activation of dopaminergic systems also accounts for amphetamine euphoria; it almost certainly accounts for cocaine euphoria and it probably accounts for opiate euphoria as well. Opiates and psychomotor stimulants clearly have many other actions which are not shared; nonshared actions must account for the well-known differences in the subjective effects of opiates and stimulants. One of the major nonshared actions is physical dependence. Opiates gain access to a major component of the circuitry mediating opiate physical dependence through opiate

  9. Addiction and brain reward and antireward pathways.

    PubMed

    Gardner, Eliot L

    2011-01-01

    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 simply encode 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) dop-aminergic 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. Postuse 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 'bio-psycho-social' model of

  10. Agent Reward Shaping for Alleviating Traffic Congestion

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan; Agogino, Adrian

    2006-01-01

    Traffic congestion problems provide a unique environment to study how multi-agent systems promote desired system level behavior. What is particularly interesting in this class of problems is that no individual action is intrinsically "bad" for the system but that combinations of actions among agents lead to undesirable outcomes, As a consequence, agents need to learn how to coordinate their actions with those of other agents, rather than learn a particular set of "good" actions. This problem is ubiquitous in various traffic problems, including selecting departure times for commuters, routes for airlines, and paths for data routers. In this paper we present a multi-agent approach to two traffic problems, where far each driver, an agent selects the most suitable action using reinforcement learning. The agent rewards are based on concepts from collectives and aim to provide the agents with rewards that are both easy to learn and that if learned, lead to good system level behavior. In the first problem, we study how agents learn the best departure times of drivers in a daily commuting environment and how following those departure times alleviates congestion. In the second problem, we study how agents learn to select desirable routes to improve traffic flow and minimize delays for. all drivers.. In both sets of experiments,. agents using collective-based rewards produced near optimal performance (93-96% of optimal) whereas agents using system rewards (63-68%) barely outperformed random action selection (62-64%) and agents using local rewards (48-72%) performed worse than random in some instances.

  11. Neurophysiological differences in reward processing in anhedonics.

    PubMed

    Padrão, Gonçalo; Mallorquí, Aida; Cucurell, David; Marco-Pallares, Josep; Rodriguez-Fornells, Antoni

    2013-03-01

    Anhedonia is characterized by a reduced capacity to experience pleasure in response to rewarding stimuli and has been considered a possible candidate endophenotype in depression and schizophrenia. However, it is still not well understood whether these reward deficits are confined to anticipatory and/or to consummatory experiences of pleasure. In the present study, we recorded electrophysiological responses (event-related brain potentials [ERPs] and oscillatory activity) to monetary gains and losses in extreme groups of anhedonic and nonanhedonic participants. The anhedonic participants showed reduced motivation to incur risky decisions, especially after monetary rewards. These sequential behavioral effects were correlated with an increased sensitivity to punishment, which psychometrically characterized the anhedonic group. In contrast, both electrophysiological measures associated with the impacts of monetary losses and gains--the feedback-related negativity (FRN) and the beta-gamma oscillatory component--clearly revealed preserved consummatory responses in anhedonic participants. However, anhedonics showed a drastic increase in frontal medial theta power after receiving the maximum monetary gain. This increase in theta oscillatory activity could be associated with an increase in conflict and cognitive control for unexpected large positive rewards, thus indexing the violation of default negative expectations built up across the task in anhedonic participants. Thus, the present results showed that participants with elevated scores on Chapman's Physical Anhedonia Scale were more sensitive to possible punishments, showed deficits in the correct integration of response outcomes in their actions, and evidenced deficits in sustaining positive expectations of future rewards. This overall pattern suggests an effect of anhedonia in the motivational aspects of approach behavior rather than in consummatory processes.

  12. Reward Allocation and Academic versus Social Orientation toward School.

    ERIC Educational Resources Information Center

    Peterson, Candida C.; Peterson, James L.

    1978-01-01

    Correlates 138 elementary school children's views about the purposes of school to their styles of reward allocation: academically motivated students allocated rewards equally to two hypothetical performers who had unequally helped a teacher perform a manual chore, while socially motivated children allocated rewards in an equity (performance-based)…

  13. Rewards, Intrinsic Motivation, and Achievement in Intact Classrooms

    ERIC Educational Resources Information Center

    Luis, Melissa Ann

    2011-01-01

    The purpose of this study was to examine the effects of performance-contingent rewards in a real-world setting, namely the sixth grade math classroom. This study is significant in that it represents a field study on the effects of rewards in the classroom. The purpose of this study was to investigate what effect, if any, the choice of a reward had…

  14. Delay Discounting of Reward in ADHD: Application in Young Children

    ERIC Educational Resources Information Center

    Wilson, Vanessa B.; Mitchell, Suzanne H.; Musser, Erica D.; Schmitt, Colleen F.; Nigg, Joel T.

    2011-01-01

    Background: A key underlying process that may contribute to attention-deficit/hyperactivity disorder (ADHD) involves alterations in reward evaluation, including assessing the relative value of immediate over delayed rewards. This study examines whether children with ADHD discount the value of delayed rewards to a greater degree than typically…

  15. Modeling the Effect of Reward Amount on Probability Discounting

    ERIC Educational Resources Information Center

    Myerson, Joel; Green, Leonard; Morris, Joshua

    2011-01-01

    The present study with college students examined the effect of amount on the discounting of probabilistic monetary rewards. A hyperboloid function accurately described the discounting of hypothetical rewards ranging in amount from $20 to $10,000,000. The degree of discounting increased continuously with amount of probabilistic reward. This effect…

  16. Rewards versus Learning: A Response to Paul Chance.

    ERIC Educational Resources Information Center

    Kohn, Alfie

    1993-01-01

    Responding to Paul Chance's November 1992 "Kappan" article on motivational value of rewards, this article argues that manipulating student behavior with either punishments or rewards is unnecessary and counterproductive. Extrinsic rewards can never buy more than short-term compliance because they are inherently controlling and…

  17. Basolateral amygdala lesions abolish mutual reward preferences in rats.

    PubMed

    Hernandez-Lallement, Julen; van Wingerden, Marijn; Schäble, Sandra; Kalenscher, Tobias

    2016-01-01

    In a recent study, we demonstrated that rats prefer mutual rewards in a Prosocial Choice Task. Here, employing the same task, we show that the integrity of basolateral amygdala was necessary for the expression of mutual reward preferences. Actor rats received bilateral excitotoxic (n=12) or sham lesions (n=10) targeting the basolateral amygdala and were subsequently tested in a Prosocial Choice Task where they could decide between rewarding ("Both Reward") or not rewarding a partner rat ("Own Reward"), either choice yielding identical reward to the actors themselves. To manipulate the social context and control for secondary reinforcement sources, actor rats were paired with either a partner rat (partner condition) or with an inanimate rat toy (toy condition). Sham-operated animals revealed a significant preference for the Both-Reward-option in the partner condition, but not in the toy condition. Amygdala-lesioned animals exhibited significantly lower Both-Reward preferences than the sham group in the partner but not in the toy condition, suggesting that basolateral amygdala was required for the expression of mutual reward preferences. Critically, in a reward magnitude discrimination task in the same experimental setup, both sham-operated and amygdala-lesioned animals preferred large over small rewards, suggesting that amygdala lesion effects were restricted to decision making in social contexts, leaving self-oriented behavior unaffected.

  18. Reward Circuitry Function in Autism during Face Anticipation and Outcomes

    ERIC Educational Resources Information Center

    Dichter, Gabriel S.; Richey, J. Anthony; Rittenberg, Alison M.; Sabatino, Antoinette; Bodfish, James W.

    2012-01-01

    The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary…

  19. 28 CFR 13.6 - Criteria for reward.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS... reward under the Atomic Weapons and Special Nuclear Materials Rewards Act must be original, and must..., acquire or export special nuclear material or atomic weapons, or (5) Loss, diversion or disposal...

  20. Managing Simultaneous Renewal: Reward Structures for School and University Faculty.

    ERIC Educational Resources Information Center

    Carnes, Nate; Schwager, Susan

    2000-01-01

    Examined the impact of rewards and reward structures for mentor teachers and university faculty engaged in preparing teachers and the ongoing professional development of veteran teachers within Professional Development Schools. School faculty cited extrinsic reward structures as inadequate, emphasizing their importance as incentives for…

  1. Extrinsic Rewards Undermine Altruistic Tendencies in 20-Month-Olds

    ERIC Educational Resources Information Center

    Warneken, Felix; Tomasello, Michael

    2008-01-01

    The current study investigated the influence of rewards on very young children's helping behavior. After 20-month-old infants received a material reward during a treatment phase, they subsequently were less likely to engage in further helping during a test phase as compared with infants who had previously received social praise or no reward at…

  2. Using Rewards To Teach Students with Disabilities: Implications for Motivation.

    ERIC Educational Resources Information Center

    Witzel, Bradley S.; Mercer, Cecil D.

    2003-01-01

    This article presents and compares current research practices surrounding the use of rewards in classroom management. A motivational model emerges of the use of extrinsic rewards with special needs learners to build intrinsic motivation. Teachers' use of praise as the focal point to multiple rewards and students' need for equity are also…

  3. 28 CFR 13.6 - Criteria for reward.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS... reward under the Atomic Weapons and Special Nuclear Materials Rewards Act must be original, and must..., acquire or export special nuclear material or atomic weapons, or (5) Loss, diversion or disposal...

  4. 28 CFR 13.6 - Criteria for reward.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS... reward under the Atomic Weapons and Special Nuclear Materials Rewards Act must be original, and must..., acquire or export special nuclear material or atomic weapons, or (5) Loss, diversion or disposal...

  5. 28 CFR 13.6 - Criteria for reward.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS... reward under the Atomic Weapons and Special Nuclear Materials Rewards Act must be original, and must..., acquire or export special nuclear material or atomic weapons, or (5) Loss, diversion or disposal...

  6. 28 CFR 13.6 - Criteria for reward.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE ATOMIC WEAPONS AND SPECIAL NUCLEAR MATERIALS REWARDS... reward under the Atomic Weapons and Special Nuclear Materials Rewards Act must be original, and must..., acquire or export special nuclear material or atomic weapons, or (5) Loss, diversion or disposal...

  7. Neural response to reward anticipation is modulated by Gray's impulsivity.

    PubMed

    Hahn, Tim; Dresler, Thomas; Ehlis, Ann-Christine; Plichta, Michael M; Heinzel, Sebastian; Polak, Thomas; Lesch, Klaus-Peter; Breuer, Felix; Jakob, Peter M; Fallgatter, Andreas J

    2009-07-15

    According to the Reinforcement Sensitivity Theory (RST), Gray's dimension of impulsivity, reflecting human trait reward sensitivity, determines the extent to which stimuli activate the Behavioural Approach System (BAS). The potential neural underpinnings of the BAS, however, remain poorly understood. In the present study, we examined the association between Gray's impulsivity as defined by the RST and event-related fMRI BOLD-response to anticipation of reward in twenty healthy human subjects in brain regions previously associated with reward processing. Anticipation of reward during a Monetary Incentive Delay Task elicited activation in key components of the human reward circuitry such as the ventral striatum, the amygdala and the orbitofrontal cortex. Interindividual differences in Gray's impulsivity accounted for a significant amount of variance of the reward-related BOLD-response in the ventral striatum and the orbitofrontal cortex. Specifically, higher trait reward sensitivity was associated with increased activation in response to cues indicating potential reward. Extending previous evidence, here we show that variance in functional brain activation during anticipation of reward is attributed to interindividual differences regarding Gray's dimension of impulsivity. Thus, trait reward sensitivity contributes to the modulation of responsiveness in major components of the human reward system which thereby display a core property of the BAS. Generally, fostering our understanding of the neural underpinnings of the association of reward-related interindividual differences in affective traits might aid researchers in quest for custom-tailored treatments of psychiatric disorders, further disentangling the complex relationship between personality traits, emotion, and health.

  8. Dopamine and glucose, obesity, and reward deficiency syndrome

    PubMed Central

    Blum, Kenneth; Thanos, Panayotis K.; Gold, Mark S.

    2014-01-01

    Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment of the brain reward circuitry resulting in a hypo-dopaminergic function. RDS involves the interactions of powerful neurotransmitters and results in abnormal craving behavior. A number of important facts which could help translate to potential therapeutic targets espoused in this focused review include: (1) consumption of alcohol in large quantities or carbohydrates binging stimulates the brain’s production of and utilization of dopamine; (2) in the meso-limbic system the enkephalinergic neurons are in close proximity, to glucose receptors; (3) highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; (4) a significant correlation between blood glucose and cerebrospinal fluid concentrations of homovanillic acid the dopamine metabolite; (5) 2-deoxyglucose (2DG), the glucose analog, in pharmacological doses is associated with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and fMRI in humans support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and for the most part, implicate the involvement of DA-modulated reward circuits in pathologic eating behaviors. Based on a consensus of neuroscience research treatment of both glucose and drug like cocaine, opiates should incorporate dopamine agonist therapy in contrast to current theories and practices that utilizes dopamine antagonistic therapy. Considering that up until now clinical utilization

  9. Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction.

    PubMed

    Blum, Kenneth; Thanos, Peter K; Oscar-Berman, Marlene; Febo, Marcelo; Baron, David; Badgaiyan, Rajendra D; Gardner, Eliot; Demetrovics, Zsolt; Fahlke, Claudia; Haberstick, Brett C; Dushaj, Kristina; Gold, Mark S

    Recently there has been debate concerning the role of brain dopamine in reward and addiction. David Nutt and associates eloquently proposed that dopamine (DA) may be central to psycho stimulant dependence and some what important for alcohol, but not important for opiates, nicotine or even cannabis. Others have also argued that surfeit theories can explain for example cocaine seeking behavior as well as non-substance-related addictive behaviors. It seems prudent to distinguish between what constitutes "surfeit" compared to" deficit" in terms of short-term (acute) and long-term (chronic) brain reward circuitry responsivity. In an attempt to resolve controversy regarding the contributions of mesolimbic DA systems to reward, we review the three main competing explanatory categories: "liking", "learning", and "wanting". They are (a) the hedonic impact -liking reward, (b) the ability to predict rewarding effects-learning and (c) the incentive salience of reward-related stimuli -wanting. In terms of acute effects, most of the evidence seems to favor the "surfeit theory". Due to preferential dopamine release at mesolimbic-VTA-caudate-accumbens loci most drugs of abuse and Reward Deficiency Syndrome (RDS) behaviors have been linked to heightened feelings of well-being and hyperdopaminergic states.The "dopamine hypotheses" originally thought to be simple, is now believed to be quite complex and involves encoding the set point of hedonic tone, encoding attention, reward expectancy, and incentive motivation. Importantly, Willuhn et al. shows that in a self-administration paradigm, (chronic) excessive use of cocaine is caused by decreased phasic dopamine signaling in the striatum. In terms of chronic addictions, others have shown a blunted responsivity at brain reward sites with food, nicotine, and even gambling behavior. Finally, we are cognizant of the differences in dopaminergic function as addiction progresses and argue that relapse may be tied to dopamine deficiency

  10. Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction

    PubMed Central

    Blum, Kenneth; Thanos, Peter K.; Oscar-Berman, Marlene; Febo, Marcelo; Baron, David; Badgaiyan, Rajendra D.; Gardner, Eliot; Demetrovics, Zsolt; Fahlke, Claudia; Haberstick, Brett C.; Dushaj, Kristina; Gold, Mark S.

    2016-01-01

    Recently there has been debate concerning the role of brain dopamine in reward and addiction. David Nutt and associates eloquently proposed that dopamine (DA) may be central to psycho stimulant dependence and some what important for alcohol, but not important for opiates, nicotine or even cannabis. Others have also argued that surfeit theories can explain for example cocaine seeking behavior as well as non-substance-related addictive behaviors. It seems prudent to distinguish between what constitutes “surfeit” compared to” deficit” in terms of short-term (acute) and long-term (chronic) brain reward circuitry responsivity. In an attempt to resolve controversy regarding the contributions of mesolimbic DA systems to reward, we review the three main competing explanatory categories: “liking”, “learning”, and “wanting”. They are (a) the hedonic impact -liking reward, (b) the ability to predict rewarding effects-learning and (c) the incentive salience of reward-related stimuli -wanting. In terms of acute effects, most of the evidence seems to favor the “surfeit theory”. Due to preferential dopamine release at mesolimbic-VTA-caudate-accumbens loci most drugs of abuse and Reward Deficiency Syndrome (RDS) behaviors have been linked to heightened feelings of well-being and hyperdopaminergic states.The “dopamine hypotheses” originally thought to be simple, is now believed to be quite complex and involves encoding the set point of hedonic tone, encoding attention, reward expectancy, and incentive motivation. Importantly, Willuhn et al. shows that in a self-administration paradigm, (chronic) excessive use of cocaine is caused by decreased phasic dopamine signaling in the striatum. In terms of chronic addictions, others have shown a blunted responsivity at brain reward sites with food, nicotine, and even gambling behavior. Finally, we are cognizant of the differences in dopaminergic function as addiction progresses and argue that relapse may be tied

  11. Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity

    PubMed Central

    van Rijn, Inge; Griffioen-Roose, Sanne; de Graaf, Cees; Smeets, Paul A. M.

    2016-01-01

    A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth and trait reward sensitivity in different hunger states. Firstly, we assessed this in data from a functional neuroimaging study (van Rijn et al., 2015), in which participants (n = 30) tasted simple solutions of a non-caloric sweetener with or without a non-sweet carbohydrate (maltodextrin) during hunger and satiety. Secondly, we expanded these analyses to regular drinks by assessing the same relationship in data from a study in which soft drinks sweetened with either sucrose or a non-caloric sweetener were administered during hunger (n = 18) (Griffioen-Roose et al., 2013). First, taste activation by the non-caloric solution/soft drink was subtracted from that by the caloric solution/soft drink to eliminate sweetness effects and retain activation induced by calories. Subsequently, this difference in taste activation was correlated with reward sensitivity as measured with the BAS drive subscale of the Behavioral Activation System (BAS) questionnaire. When participants were hungry and tasted calories from the simple solution, brain activation in the right ventral striatum (caudate), right amygdala and anterior cingulate cortex (bilaterally) correlated negatively with BAS drive scores. In contrast, when participants were satiated, taste responses correlated positively with BAS drive scores in the left caudate. These results were not replicated for soft drinks. Thus, neural responses to oral calories from maltodextrin were modulated by reward sensitivity in reward-related brain areas. This was not the case for sucrose. This may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. Also, in a familiar beverage, detection of calories per se may be

  12. Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity.

    PubMed

    van Rijn, Inge; Griffioen-Roose, Sanne; de Graaf, Cees; Smeets, Paul A M

    2015-01-01

    A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth and trait reward sensitivity in different hunger states. Firstly, we assessed this in data from a functional neuroimaging study (van Rijn et al., 2015), in which participants (n = 30) tasted simple solutions of a non-caloric sweetener with or without a non-sweet carbohydrate (maltodextrin) during hunger and satiety. Secondly, we expanded these analyses to regular drinks by assessing the same relationship in data from a study in which soft drinks sweetened with either sucrose or a non-caloric sweetener were administered during hunger (n = 18) (Griffioen-Roose et al., 2013). First, taste activation by the non-caloric solution/soft drink was subtracted from that by the caloric solution/soft drink to eliminate sweetness effects and retain activation induced by calories. Subsequently, this difference in taste activation was correlated with reward sensitivity as measured with the BAS drive subscale of the Behavioral Activation System (BAS) questionnaire. When participants were hungry and tasted calories from the simple solution, brain activation in the right ventral striatum (caudate), right amygdala and anterior cingulate cortex (bilaterally) correlated negatively with BAS drive scores. In contrast, when participants were satiated, taste responses correlated positively with BAS drive scores in the left caudate. These results were not replicated for soft drinks. Thus, neural responses to oral calories from maltodextrin were modulated by reward sensitivity in reward-related brain areas. This was not the case for sucrose. This may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. Also, in a familiar beverage, detection of calories per se may be

  13. Food reward system: current perspectives and future research needs

    PubMed Central

    Woods, Stephen C.; Pelchat, Marcia; Grigson, Patricia Sue; Stice, Eric; Farooqi, Sadaf; Khoo, Chor San; Mattes, Richard D.; Beauchamp, Gary K.

    2015-01-01

    This article reviews current research and cross-disciplinary perspectives on the neuroscience of food reward in animals and humans, examines the scientific hypothesis of food addiction, discusses methodological and terminology challenges, and identifies knowledge gaps and future research needs. Topics addressed herein include the role of reward and hedonic aspects in the regulation of food intake, neuroanatomy and neurobiology of the reward system in animals and humans, responsivity of the brain reward system to palatable foods and drugs, translation of craving versus addiction, and cognitive control of food reward. The content is based on a workshop held in 2013 by the North American Branch of the International Life Sciences Institute. PMID:26011903

  14. Food reward system: current perspectives and future research needs.

    PubMed

    Alonso-Alonso, Miguel; Woods, Stephen C; Pelchat, Marcia; Grigson, Patricia Sue; Stice, Eric; Farooqi, Sadaf; Khoo, Chor San; Mattes, Richard D; Beauchamp, Gary K

    2015-05-01

    This article reviews current research and cross-disciplinary perspectives on the neuroscience of food reward in animals and humans, examines the scientific hypothesis of food addiction, discusses methodological and terminology challenges, and identifies knowledge gaps and future research needs. Topics addressed herein include the role of reward and hedonic aspects in the regulation of food intake, neuroanatomy and neurobiology of the reward system in animals and humans, responsivity of the brain reward system to palatable foods and drugs, translation of craving versus addiction, and cognitive control of food reward. The content is based on a workshop held in 2013 by the North American Branch of the International Life Sciences Institute.

  15. Finding intrinsic rewards by embodied evolution and constrained reinforcement learning.

    PubMed

    Uchibe, Eiji; Doya, Kenji

    2008-12-01

    Understanding the design principle of reward functions is a substantial challenge both in artificial intelligence and neuroscience. Successful acquisition of a task usually requires not only rewards for goals, but also for intermediate states to promote effective exploration. This paper proposes a method for designing 'intrinsic' rewards of autonomous agents by combining constrained policy gradient reinforcement learning and embodied evolution. To validate the method, we use Cyber Rodent robots, in which collision avoidance, recharging from battery packs, and 'mating' by software reproduction are three major 'extrinsic' rewards. We show in hardware experiments that the robots can find appropriate 'intrinsic' rewards for the vision of battery packs and other robots to promote approach behaviors.

  16. A neuronal reward inequity signal in primate striatum

    PubMed Central

    van Coeverden, Charlotte R.; Schultz, Wolfram

    2015-01-01

    Primates are social animals, and their survival depends on social interactions with others. Especially important for social interactions and welfare is the observation of rewards obtained by other individuals and the comparison with own reward. The fundamental social decision variable for the comparison process is reward inequity, defined by an asymmetric reward distribution among individuals. An important brain structure for coding reward inequity may be the striatum, a component of the basal ganglia involved in goal-directed behavior. Two rhesus monkeys were seated opposite each other and contacted a touch-sensitive table placed between them to obtain specific magnitudes of reward that were equally or unequally distributed among them. Response times in one of the animals demonstrated differential behavioral sensitivity to reward inequity. A group of neurons in the striatum showed distinct signals reflecting disadvantageous and advantageous reward inequity. These neuronal signals occurred irrespective of, or in conjunction with, own reward coding. These data demonstrate that striatal neurons of macaque monkeys sense the differences between other's and own reward. The neuronal activities are likely to contribute crucial reward information to neuronal mechanisms involved in social interactions. PMID:26378202

  17. Associations among smoking, anhedonia, and reward learning in depression.

    PubMed

    Liverant, Gabrielle I; Sloan, Denise M; Pizzagalli, Diego A; Harte, Christopher B; Kamholz, Barbara W; Rosebrock, Laina E; Cohen, Andrew L; Fava, Maurizio; Kaplan, Gary B

    2014-09-01

    Depression and cigarette smoking co-occur at high rates. However, the etiological mechanisms that contribute to this relationship remain unclear. Anhedonia and associated impairments in reward learning are key features of depression, which also have been linked to the onset and maintenance of cigarette smoking. However, few studies have investigated differences in anhedonia and reward learning among depressed smokers and depressed nonsmokers. The goal of this study was to examine putative differences in anhedonia and reward learning in depressed smokers (n=36) and depressed nonsmokers (n=44). To this end, participants completed self-report measures of anhedonia and behavioral activation (BAS reward responsiveness scores) and as well as a probabilistic reward task rooted in signal detection theory, which measures reward learning (Pizzagalli, Jahn, & O'Shea, 2005). When considering self-report measures, depressed smokers reported higher trait anhedonia and reduced BAS reward responsiveness scores compared to depressed nonsmokers. In contrast to self-report measures, nicotine-satiated depressed smokers demonstrated greater acquisition of reward-based learning compared to depressed nonsmokers as indexed by the probabilistic reward task. Findings may point to a potential mechanism underlying the frequent co-occurrence of smoking and depression. These results highlight the importance of continued investigation of the role of anhedonia and reward system functioning in the co-occurrence of depression and nicotine abuse. Results also may support the use of treatments targeting reward learning (e.g., behavioral activation) to enhance smoking cessation among individuals with depression.

  18. Orquestic regulation of neurotransmitters on reward-seeking behavior

    PubMed Central

    2014-01-01

    The ventral tegmental area is strongly associated with the reward system. Dopamine is released in areas such as the nucleus accumbens and prefrontal cortex as a result of rewarding experiences such as food, sex, and neutral stimuli that become associated with them. Electrical stimulation of the ventral tegmental area or its output pathways can itself serve as a potent reward. Different drugs that increase dopamine levels are intrinsically rewarding. Although the dopaminergic system represent the cornerstone of the reward system, other neurotransmitters such as endogenous opioids, glutamate, γ-Aminobutyric acid, acetylcholine, serotonin, adenosine, endocannabinoids, orexins, galanin and histamine all affect this mesolimbic dopaminergic system. Consequently, genetic variations of neurotransmission are thought influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. Here, we discuss current evidence on the orquestic regulation of different neurotranmitters on reward-seeking behavior and its potential effect on drug addiction. PMID:25061480

  19. Reduced pupillary reward sensitivity in Parkinson’s disease

    PubMed Central

    Manohar, SG; Husain, M

    2017-01-01

    Abnormalities in reward processing may be a critical part of understanding nonmotor manifestations of Parkinson’s disease (PD). Dysfunction in dopaminergic pathways, which signal upcoming rewards, might result in altered motivation by incentives. To examine this proposal, we studied 16 patients with PD, both ON and OFF their normal dopaminergic medication, comparing them with healthy controls. Participants performed a speeded saccade task to obtain monetary rewards. Crucially, we manipulated the reward available from trial to trial, by presenting an auditory incentive precue before each saccade. The effects of incentives on pupil dilatation (an index of autonomic response) were measured. Individuals with PD showed diminished autonomic reward effects, compared with age-matched controls. When tested ON medication, pupil responses to reward increased, demonstrating that dopaminergic drugs can restore reward sensitivity. These findings reveal blunted autonomic responses to incentives in PD, which can be modulated by dopaminergic drugs. PMID:28357409

  20. Role of delay-based reward in the spatial cooperation

    NASA Astrophysics Data System (ADS)

    Wang, Xu-Wen; Nie, Sen; Jiang, Luo-Luo; Wang, Bing-Hong; Chen, Shi-Ming

    2017-01-01

    Strategy selection in games, a typical decision making, usually brings noticeable reward for players which have discounted value if the delay appears. The discounted value is measure: earning sooner with a small reward or later with a delayed larger reward. Here, we investigate effects of delayed rewards on the cooperation in structured population. It is found that delayed reward supports the spreading of cooperation in square lattice, small-world and random networks. In particular, intermediate reward differences between delays impel the highest cooperation level. Interestingly, cooperative individuals with the same delay time steps form clusters to resist the invasion of defects, and cooperative individuals with lowest delay reward survive because they form the largest clusters in the lattice.

  1. Bariatric Surgery: Risks and Rewards

    PubMed Central

    Pories, Walter J.

    2008-01-01

    Context: Over 23 million Americans are afflicted with severe obesity, i.e. their body mass index (in kilograms per square meter) values exceed 35. Of even greater concern is the association of the adiposity with comorbidities such as diabetes, hypertension, cardiopulmonary failure, asthma, pseudotumor cerebri, infertility, and crippling arthritis. Objective: Diets, exercise, behavioral modification, and drugs are not effective in these individuals. This article examines the effect of surgery on the control of the weight and the comorbidities, as well as the safety of these operations. Interventions: Although the article focuses on the outcomes of the three most commonly performed operations, i.e. adjustable gastric banding, the gastric bypass, and the biliopancreatic bypass with duodenal switch, it aims for perspective with the inclusion of abandoned and current investigational procedures, a review of the complications, and an emphasis on the appropriate selection of patients. Positions: Ample evidence, including controlled randomized studies, now document that bariatric surgery produces durable weight loss exceeding 100 lb (46 kg), full and long-term remission of type 2 diabetes in over 80% with salutary effects on the other comorbidities as well with significant reductions in all-cause mortality. Although the severely obese present with serious surgical risks, bariatric surgery is performed safely with a 0.35% 90-d mortality in Centers of Excellence throughout the United States—similar to the complication rates after cholecystectomy. Conclusions: Until better approaches become available, bariatric surgery is the therapy of choice for patients with severe obesity. PMID:18987275

  2. Side-specific reward memories in honeybees.

    PubMed

    Gil, Mariana; Menzel, Randolf; De Marco, Rodrigo J

    2009-07-01

    We report a hitherto unknown form of side-specific learning in honeybees. We trained bees individually by coupling gustatory and mechanical stimulation of each antenna with either increasing or decreasing volumes of sucrose solution offered to the animal's proboscis along successive learning trials. Next, we examined their proboscis extension response (PER) after stimulation of each antenna 1, 2, 3, and 24 h after training. The bees extended their proboscises earlier after stimulation of the antenna that had been coupled with increasing volumes than after stimulation of the antenna that had been coupled with decreasing volumes, thereby revealing short- and long-term side differences in the bees' PE reaction time. The bees' reaction time correlated well with the reaction time of the muscles M17. Long-term side differences in reaction time were prevented by repetitive antennal stimulation. Mechanosensory input was indispensable and sufficient for revealing side differences in reaction time. Such differences were specific to the gustatory input that the bees experienced during training. Our results show that side differences in the bees' PE reaction time depend upon the activation of side-specific reward memories. These memories are formed via the combined effect of a specific property of reward, i.e., that its magnitude increases or decreases over time, and side information seemingly relying on mechanosensory input. We present a learning procedure suitable to study reward learning in honeybees, which includes precise behavioral measures, physiological correlates of behavior, and within-animal controls. This procedure will prove fruitful in pharmacological and electrophysiological analyses of the neural substrates underlying reward memories in honeybees.

  3. Reward system and temporal pole contributions to affective evaluation during a first person shooter video game

    PubMed Central

    2011-01-01

    Background Violent content in video games evokes many concerns but there is little research concerning its rewarding aspects. It was demonstrated that playing a video game leads to striatal dopamine release. It is unclear, however, which aspects of the game cause this reward system activation and if violent content contributes to it. We combined functional Magnetic Resonance Imaging (fMRI) with individual affect measures to address the neuronal correlates of violence in a video game. Results Thirteen male German volunteers played a first-person shooter game (Tactical Ops: Assault on Terror) during fMRI measurement. We defined success as eliminating opponents, and failure as being eliminated themselves. Affect was measured directly before and after game play using the Positive and Negative Affect Schedule (PANAS). Failure and success events evoked increased activity in visual cortex but only failure decreased activity in orbitofrontal cortex and caudate nucleus. A negative correlation between negative affect and responses to failure was evident in the right temporal pole (rTP). Conclusions The deactivation of the caudate nucleus during failure is in accordance with its role in reward-prediction error: it occurred whenever subject missed an expected reward (being eliminated rather than eliminating the opponent). We found no indication that violence events were directly rewarding for the players. We addressed subjective evaluations of affect change due to gameplay to study the reward system. Subjects reporting greater negative affect after playing the game had less rTP activity associated with failure. The rTP may therefore be involved in evaluating the failure events in a social context, to regulate the players' mood. PMID:21749711

  4. Hypoalgesia Induced by Reward Devaluation in Rats.

    PubMed

    Jiménez-García, Ana María; Ruíz-Leyva, Leandro; Cendán, Cruz Miguel; Torres, Carmen; Papini, Mauricio R; Morón, Ignacio

    2016-01-01

    Reduced sensitivity to physical pain (hypoalgesia) has been reported after events involving reward devaluation. Reward devaluation was implemented in a consummatory successive negative contrast (cSNC) task. Food-deprived Wistar rats had access to 32% sucrose during 16 sessions followed by access to 4% sucrose during 3 additional sessions. An unshifted control group had access to 4% sucrose throughout the 19 sessions. Pain sensitivity was measured using von Frey filaments (Experiment 1) and Hargreaves thermal stimuli (Experiment 2) in pretraining baseline, 5 min, and 300 min after either the first (session 17) or second (session 18) devaluation session in the cSNC situation. Sucrose consumption was lower in downshifted groups relative to unshifted groups during postshift sessions-the cSNC effect. Hypoalgesia was observed in downshifted groups relative to unshifted controls when pain sensitivity was assessed 5 min after either the first or second devaluation session, regardless of the pain sensitivity test used. Both pain sensitivity tests yielded evidence of hypoalgesia 300 min after the second downshift session, but not 300 min after the first devaluation session. Whereas hypoalgesia was previously shown only after the second devaluation session, here we report evidence of hypoalgesia after both the first and second devaluation sessions using mechanical and thermal nociceptive stimuli. Moreover, the hypoalgesia observed 300 min after the second devaluation session in both experiments provides unique evidence of the effects of reward loss on sensitivity to physical pain 5 hours after the loss episode. The underlying neurobehavioral mechanisms remain to be identified.

  5. Studying Food Reward and Motivation in Humans

    PubMed Central

    Ziauddeen, Hisham; Subramaniam, Naresh; Cambridge, Victoria C.; Medic, Nenad; Farooqi, Ismaa Sadaf; Fletcher, Paul C.

    2014-01-01

    A key challenge in studying reward processing in humans is to go beyond subjective self-report measures and quantify different aspects of reward such as hedonics, motivation, and goal value in more objective ways. This is particularly relevant for the understanding of overeating and obesity as well as their potential treatments. In this paper are described a set of measures of food-related motivation using handgrip force as a motivational measure. These methods can be used to examine changes in food related motivation with metabolic (satiety) and pharmacological manipulations and can be used to evaluate interventions targeted at overeating and obesity. However to understand food-related decision making in the complex food environment it is essential to be able to ascertain the reward goal values that guide the decisions and behavioral choices that people make. These values are hidden but it is possible to ascertain them more objectively using metrics such as the willingness to pay and a method for this is described. Both these sets of methods provide quantitative measures of motivation and goal value that can be compared within and between individuals. PMID:24686284

  6. Studying food reward and motivation in humans.

    PubMed

    Ziauddeen, Hisham; Subramaniam, Naresh; Cambridge, Victoria C; Medic, Nenad; Farooqi, Ismaa Sadaf; Fletcher, Paul C

    2014-03-19

    A key challenge in studying reward processing in humans is to go beyond subjective self-report measures and quantify different aspects of reward such as hedonics, motivation, and goal value in more objective ways. This is particularly relevant for the understanding of overeating and obesity as well as their potential treatments. In this paper are described a set of measures of food-related motivation using handgrip force as a motivational measure. These methods can be used to examine changes in food related motivation with metabolic (satiety) and pharmacological manipulations and can be used to evaluate interventions targeted at overeating and obesity. However to understand food-related decision making in the complex food environment it is essential to be able to ascertain the reward goal values that guide the decisions and behavioral choices that people make. These values are hidden but it is possible to ascertain them more objectively using metrics such as the willingness to pay and a method for this is described. Both these sets of methods provide quantitative measures of motivation and goal value that can be compared within and between individuals.

  7. Rewarding safe behavior: strategies for change.

    PubMed

    Fell-Carlson, Deborah

    2004-12-01

    Effective, sustainable safety incentives are integrated into a performance management system designed to encourage long term behavior change. Effective incentive program design integrates the fundamental considerations of compensation (i.e., valence, instrumentality, expectancy, equity) with behavior change theory in the context of a strong merit based performance management system. Clear expectations are established and communicated from the time applicants apply for the position. Feedback and social recognition are leveraged and used as rewards, in addition to financial incentives built into the compensation system and offered periodically as short term incentives. Rewards are tied to specific objectives intended to influence specific behaviors. Objectives are designed to challenge employees, providing opportunities to grow and enhance their sense of belonging. Safety contests and other awareness activities are most effective when used to focus safety improvement efforts on specific behaviors or processes, for a predetermined period of time, in the context of a comprehensive safety system. Safety incentive programs designed around injury outcomes can result in unintended, and undesirable, consequences. Safety performance can be leveraged by integrating safety into corporate cultural indicators. Symbols of safety remind employees of corporate safety goals and objectives (e.g., posted safety goals and integrating safety into corporate mission and vision). Rites and ceremonies provide opportunities for social recognition and feedback and demonstrate safety is a corporate value. Feedback opportunities, rewards, and social recognition all provide content for corporate legends, those stories embellished over time, that punctuate the overall system of organizational norms, and provide examples of the organizational safety culture in action.

  8. Association between reward-related activation in the ventral striatum and trait reward sensitivity is moderated by dopamine transporter genotype.

    PubMed

    Hahn, Tim; Heinzel, Sebastian; Dresler, Thomas; Plichta, Michael M; Renner, Tobias J; Markulin, Falko; Jakob, Peter M; Lesch, Klaus-Peter; Fallgatter, Andreas J

    2011-10-01

    The impact of individual differences on human reward processing has been a focus of research in recent years, particularly, as they are associated with a variety of neuropsychiatric diseases including addiction and attention-deficit/hyperactivity disorder. Studies exploring the neural basis of individual differences in reward sensitivity have consistently implicated the ventral striatum (VS) as a core component of the human reward system. However, the mechanisms of dopaminergic neurotransmission underlying ventral striatal activation as well as trait reward sensitivity remain speculative. We addressed this issue by investigating the triadic interplay between VS reactivity during reward anticipation using functional magnetic resonance imaging, trait reward sensitivity, and dopamine (DA) transporter genotype (40-bp 3'VNTR of DAT, SLC6A3) affecting synaptic DA neurotransmission. Our results show that DAT variation moderates the association between VS-reactivity and trait reward sensitivity. Specifically, homozygote carriers of the DAT 10-repeat allele exhibit a strong positive correlation between reward sensitivity and reward-related VS activity whereas this relationship is absent in the DAT 9-repeat allele carriers. We discuss the possibility that this moderation of VS-trait relation might arise from DAT-dependent differences in DA availability affecting synaptic plasticity within the VS. Generally, studying the impact of dopaminergic gene variations on the relation between reward-related brain activity and trait reward sensitivity might facilitate the investigation of complex mechanisms underlying disorders linked to dysregulation of DA neurotransmission.

  9. Extinction Can Reduce the Impact of Reward Cues on Reward-Seeking Behavior.

    PubMed

    Lovibond, Peter F; Satkunarajah, Michelle; Colagiuri, Ben

    2015-07-01

    Reward-associated cues are thought to promote relapse after treatment of appetitive disorders such as drug-taking, binge eating, and gambling. This process has been modelled in the laboratory using a Pavlovian-instrumental transfer (PIT) design in which Pavlovian cues facilitate instrumental reward-directed action. Attempts to reduce facilitation by cue exposure (extinction) have produced mixed results. We tested the effect of extinction in a recently developed PIT procedure using a natural reward, chocolate, in human participants. Facilitation of instrumental responding was only observed in participants who were aware of the Pavlovian contingencies. Pavlovian extinction successfully reduced, but did not completely eliminate, expectancy of reward and facilitation of instrumental responding. The results indicate that exposure can reduce the ability of cues to promote reward-directed behavior in the laboratory. However, the residual potency of extinguished cues means that additional active strategies may be needed in clinical practice to train patients to resist the impact of these cues in their environment.

  10. Developmental changes in the reward positivity: an electrophysiological trajectory of reward processing.

    PubMed

    Lukie, Carmen N; Montazer-Hojat, Somayyeh; Holroyd, Clay B

    2014-07-01

    Children and adolescents learn to regulate their behavior by utilizing feedback from the environment but exactly how this ability develops remains unclear. To investigate this question, we recorded the event-related brain potential (ERP) from children (8-13 years), adolescents (14-17 years) and young adults (18-23 years) while they navigated a "virtual maze" in pursuit of monetary rewards. The amplitude of the reward positivity, an ERP component elicited by feedback stimuli, was evaluated for each age group. A current theory suggests the reward positivity is produced by the impact of reinforcement learning signals carried by the midbrain dopamine system on anterior cingulate cortex, which utilizes the signals to learn and execute extended behaviors. We found that the three groups produced a reward positivity of comparable size despite relatively longer ERP component latencies for the children, suggesting that the reward processing system reaches maturity early in development. We propose that early development of the midbrain dopamine system facilitates the development of extended goal-directed behaviors in anterior cingulate cortex.

  11. Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement.

    PubMed

    Noonan, M P; Kolling, N; Walton, M E; Rushworth, M F S

    2012-04-01

    The orbitofrontal cortex and adjacent ventromedial prefrontal cortex carry reward representations and mediate flexible behaviour when circumstances change. Here we review how recent experiments in humans and macaques have confirmed the existence of a major difference between the functions of the ventromedial prefrontal cortex and adjacent medial orbitofrontal cortex (mOFC) on the one hand and the lateral orbitofrontal cortex (lOFC) on the other. These differences, however, may not be best accounted for in terms of specializations for reward and error/punishment processing as is commonly assumed. Instead we argue that both lesion and functional magnetic resonance imaging studies reveal that the lOFC is concerned with the assignment of credit for both reward and error outcomes to the choice of specific stimuli and with the linking of specific stimulus representations to representations of specific types of reward outcome. By contrast, we argue that the ventromedial prefrontal cortex/mOFC is concerned with evaluation, value-guided decision-making and maintenance of a choice over successive decisions. Despite the popular view that they cause perseveration of behaviour and inability to inhibit repetition of a previously made choice, we found that lesions in neither orbitofrontal subdivision caused perseveration. On the contrary, lesions in the lOFC made animals switch more rapidly between choices when they were finding it difficult to assign reward values to choices. Lesions in the mOFC caused animals to lose their normal predisposition to repeat previously successful choices, suggesting that the mOFC does not just mediate value comparison in choice but also facilitates maintenance of the same choice if it has been successful.

  12. Striatal dopamine, reward, and decision making in schizophrenia

    PubMed Central

    Deserno, Lorenz; Schlagenhauf, Florian; Heinz, Andreas

    2016-01-01

    Elevated striatal dopamine function is one of the best-established findings in schizophrenia. In this review, we discuss causes and consequences of this striata! dopamine alteration. We first summarize earlier findings regarding striatal reward processing and anticipation using functional neuroimaging. Secondly, we present a series of recent studies that are exemplary for a particular research approach: a combination of theory-driven reinforcement learning and decision-making tasks in combination with computational modeling and functional neuroimaging. We discuss why this approach represents a promising tool to understand underlying mechanisms of symptom dimensions by dissecting the contribution of multiple behavioral control systems working in parallel. We also discuss how it can advance our understanding of the neurobiological implementation of such functions. Thirdly, we review evidence regarding the topography of dopamine dysfunction within the striatum. Finally, we present conclusions and outline important aspects to be considered in future studies. PMID:27069382

  13. Striatal dopamine, reward, and decision making in schizophrenia.

    PubMed

    Deserno, Lorenz; Schlagenhauf, Florian; Heinz, Andreas

    2016-03-01

    Elevated striatal dopamine function is one of the best-established findings in schizophrenia. In this review, we discuss causes and consequences of this striata! dopamine alteration. We first summarize earlier findings regarding striatal reward processing and anticipation using functional neuroimaging. Secondly, we present a series of recent studies that are exemplary for a particular research approach: a combination of theory-driven reinforcement learning and decision-making tasks in combination with computational modeling and functional neuroimaging. We discuss why this approach represents a promising tool to understand underlying mechanisms of symptom dimensions by dissecting the contribution of multiple behavioral control systems working in parallel. We also discuss how it can advance our understanding of the neurobiological implementation of such functions. Thirdly, we review evidence regarding the topography of dopamine dysfunction within the striatum. Finally, we present conclusions and outline important aspects to be considered in future studies.

  14. Differentiating neural reward responsiveness in autism versus ADHD.

    PubMed

    Kohls, Gregor; Thönessen, Heike; Bartley, Gregory K; Grossheinrich, Nicola; Fink, Gereon R; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2014-10-01

    Although attention deficit hyperactivity disorders (ADHD) and autism spectrum disorders (ASD) share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC). A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ASD. Shared dysfunction was characterized by fronto-striato-parietal hypoactivation in both clinical groups when money was at stake. Interestingly, lower neural activation within parietal circuitry was associated with higher autistic traits across the entire study sample. In sum, the present findings concur with the assumption that both ASD and ADHD display distinct and shared neural dysfunction in response to reward.

  15. Placebo Intervention Enhances Reward Learning in Healthy Individuals

    PubMed Central

    Turi, Zsolt; Mittner, Matthias; Paulus, Walter; Antal, Andrea

    2017-01-01

    According to the placebo-reward hypothesis, placebo is a reward-anticipation process that increases midbrain dopamine (DA) levels. Reward-based learning processes, such as reinforcement learning, involves a large part of the DA-ergic network that is also activated by the placebo intervention. Given the neurochemical overlap between placebo and reward learning, we investigated whether verbal instructions in conjunction with a placebo intervention are capable of enhancing reward learning in healthy individuals by using a monetary reward-based reinforcement-learning task. Placebo intervention was performed with non-invasive brain stimulation techniques. In a randomized, triple-blind, cross-over study we investigated this cognitive placebo effect in healthy individuals by manipulating the participants’ perceived uncertainty about the intervention’s efficacy. Volunteers in the purportedly low- and high-uncertainty conditions earned more money, responded more quickly and had a higher learning rate from monetary rewards relative to baseline. Participants in the purportedly high-uncertainty conditions showed enhanced reward learning, and a model-free computational analysis revealed a higher learning rate from monetary rewards compared to the purportedly low-uncertainty and baseline conditions. Our results indicate that the placebo response is able to enhance reward learning in healthy individuals, opening up exciting avenues for future research in placebo effects on other cognitive functions. PMID:28112207

  16. A test of the reward-value hypothesis.

    PubMed

    Smith, Alexandra E; Dalecki, Stefan J; Crystal, Jonathon D

    2017-03-01

    Rats retain source memory (memory for the origin of information) over a retention interval of at least 1 week, whereas their spatial working memory (radial maze locations) decays within approximately 1 day. We have argued that different forgetting functions dissociate memory systems. However, the two tasks, in our previous work, used different reward values. The source memory task used multiple pellets of a preferred food flavor (chocolate), whereas the spatial working memory task provided access to a single pellet of standard chow-flavored food at each location. Thus, according to the reward-value hypothesis, enhanced performance in the source memory task stems from enhanced encoding/memory of a preferred reward. We tested the reward-value hypothesis by using a standard 8-arm radial maze task to compare spatial working memory accuracy of rats rewarded with either multiple chocolate or chow pellets at each location using a between-subjects design. The reward-value hypothesis predicts superior accuracy for high-valued rewards. We documented equivalent spatial memory accuracy for high- and low-value rewards. Importantly, a 24-h retention interval produced equivalent spatial working memory accuracy for both flavors. These data are inconsistent with the reward-value hypothesis and suggest that reward value does not explain our earlier findings that source memory survives unusually long retention intervals.

  17. Altered subjective reward valuation among female heavy marijuana users.

    PubMed

    Hefner, Kathryn R; Starr, Mark J

    2017-02-01

    Maladaptive decision-making is a cardinal feature of drug use, contributing to ongoing use, and reflecting alterations in how drug users assess uncertain reward value. Accumulating evidence indicates the consequences of heavy marijuana use are worse for female versus male animals and humans, but research assessing sex differences in reward-related decision-making among marijuana users remains scarce. We examined sex differences in the subjective valuation of certain and uncertain rewards among heavy marijuana users (52; 26 male and 26 female) and controls (52; 26 male and 26 female). We offered male and female heavy marijuana users and controls monetary rewards of certain and uncertain (probabilistic) values. We measured how preferences for uncertain rewards varied by the objective value of those rewards, moderators of reward uncertainty, Marijuana Group and Sex. Men were more sensitive to changes in the objective value of uncertain rewards than women. However, this effect of Sex differed by Marijuana Group. Female heavy marijuana users were more sensitive to changes in uncertain reward value, particularly when the "stakes" were high (i.e., greater difference between potential uncertain rewards), than female controls. Female heavy marijuana users' sensitivity to changes in the value of high stakes uncertain rewards was comparable to male marijuana users and controls. In contrast, male marijuana users' sensitivity to changes in the value of high stakes uncertain rewards did not differ from male controls. These results suggest sex differences in sensitivity to high risk rewards may be one pathway contributing to severer consequences of heavy marijuana use among women. (PsycINFO Database Record

  18. Pain and suicidality: insights from reward and addiction neuroscience.

    PubMed

    Elman, Igor; Borsook, David; Volkow, Nora D

    2013-10-01

    Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system's role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain- and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other "reward deficiency syndromes" and a new proposal for "enhanced anti-reward syndromes". We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk.

  19. Pain and suicidality: Insights from reward and addiction neuroscience

    PubMed Central

    Elman, Igor; Borsook, David; Volkow, Nora D.

    2016-01-01

    Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system’s role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain-and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other “reward deficiency syndromes” and a new proposal for “enhanced anti-reward syndromes”. We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. PMID:23827972

  20. Inferring reward prediction errors in patients with schizophrenia: a dynamic reward task for reinforcement learning.

    PubMed

    Li, Chia-Tzu; Lai, Wen-Sung; Liu, Chih-Min; Hsu, Yung-Fong

    2014-01-01

    Abnormalities in the dopamine system have long been implicated in explanations of reinforcement learning and psychosis. The updated reward prediction error (RPE)-a discrepancy between the predicted and actual rewards-is thought to be encoded by dopaminergic neurons. Dysregulation of dopamine systems could alter the appraisal of stimuli and eventually lead to schizophrenia. Accordingly, the measurement of RPE provides a potential behavioral index for the evaluation of brain dopamine activity and psychotic symptoms. Here, we assess two features potentially crucial to the RPE process, namely belief formation and belief perseveration, via a probability learning task and reinforcement-learning modeling. Forty-five patients with schizophrenia [26 high-psychosis and 19 low-psychosis, based on their p1 and p3 scores in the positive-symptom subscales of the Positive and Negative Syndrome Scale (PANSS)] and 24 controls were tested in a feedback-based dynamic reward task for their RPE-related decision making. While task scores across the three groups were similar, matching law analysis revealed that the reward sensitivities of both psychosis groups were lower than that of controls. Trial-by-trial data were further fit with a reinforcement learning model using the Bayesian estimation approach. Model fitting results indicated that both psychosis groups tend to update their reward values more rapidly than controls. Moreover, among the three groups, high-psychosis patients had the lowest degree of choice perseveration. Lumping patients' data together, we also found that patients' perseveration appears to be negatively correlated (p = 0.09, trending toward significance) with their PANSS p1 + p3 scores. Our method provides an alternative for investigating reward-related learning and decision making in basic and clinical settings.

  1. Striatal development in autism: repetitive behaviors and the reward circuitry

    PubMed Central

    Kohls, Gregor; Yerys, Benjamin; Schultz, Robert T.

    2016-01-01

    subcortical targets within the frontostriatal behavior control loops that are recognized as likely subserving RRBIs4. This current study is a follow up of this same group's earlier work showing cross sectional differences in growth trajectory. While several labs have previously reported enlargement of the caudate nucleus in ASD, this current study is the first to make repeat morphology measurements, thus overcoming limitations associated with cross sectional analyses. This study involved 86 seven to seventeen year old cases and controls who had 2 MRI anatomical scans approximately 2 and a half years apart on average, allowing a direct test of differential striatal growth. The rate of basal ganglia growth was correlated with the severity of RRBIs as assessed by parent interview at the time of the first MRI scan, corroborating earlier work on the role of the striatum in repetitive behaviors among children with ASD. Specifically the caudate nucleus showed a growth rate in ASD that was twice as high as the growth rate in TDC (i.e., 4.6% vs. 2.3%). This was independent of overall brain growth, use of psychotropic medications, or other major confounds. Most importantly, more severe RRBIs early in life, particularly insistence on sameness behaviors, such as avoiding trivial changes in routines and environments as well as adhering to compulsions and rituals, were related to faster striatal growth between average ages of about 9 and 12 year old, with large effect sizes (e.g., caudate nucleus: Cohen's d = 0.86). While Langen et al. discuss several complementary explanations for their findings, they conclude that the divergent trajectory of caudate development in relation to RRBIs most likely results from early, and possibly continuing, patterns of repetitive behaviors that shape striatal development – not the other way around. This new set of data elegantly adds to the notion that the striatum plays a central role in core ASD phenomenology6. However, one question lingers: what cause

  2. Whole-Brain Neural Dynamics of Probabilistic Reward Prediction.

    PubMed

    Bach, Dominik R; Symmonds, Mkael; Barnes, Gareth; Dolan, Raymond J

    2017-04-05

    Predicting future reward is paramount to performing an optimal action. Although a number of brain areas are known to encode such predictions, a detailed account of how the associated representations evolve over time is lacking. Here, we address this question using human magnetoencephalography (MEG) and multivariate analyses of instantaneous activity in reconstructed sources. We overtrained participants on a simple instrumental reward learning task where geometric cues predicted a distribution of possible rewards, from which a sample was revealed 2000 ms later. We show that predicted mean reward (i.e., expected value), and predicted reward variability (i.e., economic risk), are encoded distinctly. Early on, representations of mean reward are seen in parietal and visual areas, and later in frontal regions with orbitofrontal cortex emerging last. Strikingly, an encoding of reward variability emerges simultaneously in parietal/sensory and frontal sources and later than mean reward encoding. An orbitofrontal variability encoding emerged around the same time as that seen for mean reward. Crucially, cross-prediction showed that mean reward and variability representations are distinct and also revealed that instantaneous representations become more stable over time. Across sources, the best fitting metric for variability signals was coefficient of variation (rather than SD or variance), but distinct best metrics were seen for individual brain regions. Our data demonstrate how a dynamic encoding of probabilistic reward prediction unfolds in the brain both in time and space.SIGNIFICANCE STATEMENT Predicting future reward is paramount to optimal behavior. To gain insight into the underlying neural computations, we investigate how reward representations in the brain arise over time. Using magnetoencephalography, we show that a representation of predicted mean reward emerges early in parietal/sensory regions and later in frontal cortex. In contrast, predicted reward variability

  3. Neural basis of reward anticipation and its genetic determinants.

    PubMed

    Jia, Tianye; Macare, Christine; Desrivières, Sylvane; Gonzalez, Dante A; Tao, Chenyang; Ji, Xiaoxi; Ruggeri, Barbara; Nees, Frauke; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia J; Dove, Rachel; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny A; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lemaitre, Hervé; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Poline, Jean-Baptiste; Rietschel, Marcella; Robbins, Trevor; Smolka, Michael N; Müller, Christian P; Feng, Jianfeng; Rothenfluh, Adrian; Flor, Herta; Schumann, Gunter

    2016-04-05

    Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature.

  4. Neural basis of reward anticipation and its genetic determinants

    PubMed Central

    Jia, Tianye; Macare, Christine; Desrivières, Sylvane; Gonzalez, Dante A.; Tao, Chenyang; Ji, Xiaoxi; Ruggeri, Barbara; Nees, Frauke; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; Bromberg, Uli; Büchel, Christian; Conrod, Patricia J.; Dove, Rachel; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny A.; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lemaitre, Hervé; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Poline, Jean-Baptiste; Rietschel, Marcella; Robbins, Trevor; Müller, Christian P.; Feng, Jianfeng; Rothenfluh, Adrian; Flor, Herta; Schumann, Gunter

    2016-01-01

    Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila. Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature. PMID:27001827

  5. Differential effect of reward and punishment on procedural learning.

    PubMed

    Wächter, Tobias; Lungu, Ovidiu V; Liu, Tao; Willingham, Daniel T; Ashe, James

    2009-01-14

    Reward and punishment are potent modulators of associative learning in instrumental and classical conditioning. However, the effect of reward and punishment on procedural learning is not known. The striatum is known to be an important locus of reward-related neural signals and part of the neural substrate of procedural learning. Here, using an implicit motor learning task, we show that reward leads to enhancement of learning in human subjects, whereas punishment is associated only with improvement in motor performance. Furthermore, these behavioral effects have distinct neural substrates with the learning effect of reward being mediated through the dorsal striatum and the performance effect of punishment through the insula. Our results suggest that reward and punishment engage separate motivational systems with distinctive behavioral effects and neural substrates.

  6. Effects of monetary reward and punishment on information checking behaviour.

    PubMed

    Li, Simon Y W; Cox, Anna L; Or, Calvin; Blandford, Ann

    2016-03-01

    Two experiments were conducted to examine whether checking one's own work can be motivated by monetary reward and punishment. Participants were randomly assigned to one of three conditions: a flat-rate payment for completing the task (Control); payment increased for error-free performance (Reward); payment decreased for error performance (Punishment). Experiment 1 (N = 90) was conducted with liberal arts students, using a general data-entry task. Experiment 2 (N = 90) replicated Experiment 1 with clinical students and a safety-critical 'cover story' for the task. In both studies, Reward and Punishment resulted in significantly fewer errors, more frequent and longer checking, than Control. No such differences were obtained between the Reward and Punishment conditions. It is concluded that error consequences in terms of monetary reward and punishment can result in more accurate task performance and more rigorous checking behaviour than errors without consequences. However, whether punishment is more effective than reward, or vice versa, remains inconclusive.

  7. The role of the neural reward system in attention selection.

    PubMed

    Soder, Heather E; de Dios, Constanza; Potts, Geoffrey F

    2016-07-06

    The prefrontal cortex may play a role in attention selection using motivational information from the mesotelencephalic dopamine system, a neural system that responds to reward prediction violations. If so, neural indices of attention selection and reward prediction violation should have overlapping spatiotemporal distributions. Attention selection elicits a frontal event-related potential component around 200-300 ms, the frontal selection positivity. A component with similar spatiotemporal characteristics, the reward positivity is elicited in reward prediction designs to outcomes that are better than expected. The current study used dense sensor array recording in a sample of 41 participants performing visual oddball (attention) and a reward prediction 'slot machine-like' design to compare the spatiotemporal distributions of the frontal selection positivity and the reward positivity. The components did not differ in their peak latencies and had overlapping scalp topographies, supporting the hypothesis that these positivities represent attachment of incentive salience to perceptual representations in the prefrontal cortex.

  8. A Positive Affective Neuroendocrinology Approach to Reward and Behavioral Dysregulation

    PubMed Central

    Welker, Keith M.; Gruber, June; Mehta, Pranjal H.

    2015-01-01

    Emerging lines of research suggest that both testosterone and maladaptive reward processing can modulate behavioral dysregulation. Yet, to date, no integrative account has been provided that systematically explains neuroendocrine function, dysregulation of reward, and behavioral dysregulation in a unified perspective. This is particularly important given specific neuroendocrine systems are potential mechanisms underlying and giving rise to reward-relevant behaviors. In this review, we propose a forward-thinking approach to study the mechanisms of reward and behavioral dysregulation from a positive affective neuroendocrinology (PANE) perspective. This approach holds that testosterone increases reward processing and motivation, which increase the likelihood of behavioral dysregulation. Additionally, the PANE framework holds that reward processing mediates the effects of testosterone on behavioral dysregulation. We also explore sources of potential sex differences and the roles of age, cortisol, and individual differences within the PANE framework. Finally, we discuss future prospects for research questions and methodology in the emerging field of affective neuroendocrinology. PMID:26191007

  9. Attentuation of the differential outcomes effect by extraneous reward.

    PubMed

    White, K Geoffrey; Millar, Jessica Grace

    2014-10-01

    The reinforcement context model for performance in delayed matching to sample tasks (White and Brown, 2014) predicts the course of forgetting based on the assumption that rewards for extraneous behavior compete with rewards for accurate matching and increase as a linear function of retention-interval duration. In the differential outcomes effect, greater matching accuracy occurs when correct choices produce different outcomes, which the model assumes have greater reward effectiveness than same outcomes. The model was tested in the present experiment with pigeons by arranging an additional task during the retention interval of a delayed matching to sample task, center-key pecking rewarded by food delivered at variable intervals. This additional source of extraneous reward resulted in attenuation of the differential outcomes effect as predicted by the model. The model was supported by satisfactory quantitative fits to the forgetting functions for same and different outcome conditions with and without additional extraneous reward.

  10. Positive emotions and brain reward circuits in chronic pain.

    PubMed

    Navratilova, Edita; Morimura, Kozo; Xie, Jennifer Y; Atcherley, Christopher W; Ossipov, Michael H; Porreca, Frank

    2016-06-01

    Chronic pain is an important public health problem that negatively impacts the quality of life of affected individuals and exacts enormous socioeconomic costs. Chronic pain is often accompanied by comorbid emotional disorders including anxiety, depression, and possibly anhedonia. The neural circuits underlying the intersection of pain and pleasure are not well understood. We summarize recent human and animal investigations and demonstrate that aversive aspects of pain are encoded in brain regions overlapping with areas processing reward and motivation. We highlight findings revealing anatomical and functional alterations of reward/motivation circuits in chronic pain. Finally, we review supporting evidence for the concept that pain relief is rewarding and activates brain reward/motivation circuits. Adaptations in brain reward circuits may be fundamental to the pathology of chronic pain. Knowledge of brain reward processing in the context of pain could lead to the development of new therapeutics for the treatment of emotional aspects of pain and comorbid conditions.

  11. Translational Assessment of Reward and Motivational Deficits in Psychiatric Disorders

    PubMed Central

    Der-Avakian, Andre; Barnes, Samuel A.

    2016-01-01

    Deficits in reward and motivation are common symptoms characterizing several psychiatric and neurological disorders. Such deficits may include anhedonia, defined as loss of pleasure, as well as impairments in anticipatory pleasure, reward valuation, motivation/effort, and reward learning. This chapter describes recent advances in the development of behavioral tasks used to assess different aspects of reward processing in both humans and non-human animals. While earlier tasks were generally developed independently with limited cross-species correspondence, a newer generation of translational tasks has emerged that are theoretically and procedurally analogous across species and allow parallel testing, data analyses, and interpretation between human and rodent behaviors. Such enhanced conformity between cross-species tasks will facilitate investigation of the neurobiological mechanisms underlying discrete reward and motivated behaviors and is expected to improve our understanding and treatment of neuropsychiatric disorders characterized by reward and motivation deficits. PMID:26873017

  12. Extrinsic Rewards Diminish Costly Sharing in 3-Year-Olds.

    PubMed

    Ulber, Julia; Hamann, Katharina; Tomasello, Michael

    2016-07-01

    Two studies investigated the influence of external rewards and social praise in young children's fairness-related behavior. The motivation of ninety-six 3-year-olds' to equalize unfair resource allocations was measured in three scenarios (collaboration, windfall, and dictator game) following three different treatments (material reward, verbal praise, and neutral response). In all scenarios, children's willingness to engage in costly sharing was negatively influenced when they had received a reward for equal sharing during treatment than when they had received praise or no reward. The negative effect of material rewards was not due to subjects responding in kind to their partner's termination of rewards. These results provide new evidence for the intrinsic motivation of prosociality-in this case, costly sharing behavior-in preschool children.

  13. Differential Effect of Reward and Punishment on Procedural Learning

    PubMed Central

    Wächter, Tobias; Lungu, Ovidiu V.; Liu, Tao; Willingham, Daniel T.; Ashe, James

    2009-01-01

    Reward and punishment are potent modulators of associative learning in instrumental and classical conditioning. However, the effect of reward and punishment on procedural learning is not known. The striatum is known to be an important locus of reward-related neural signals and part of the neural substrate of procedural learning. Here, using an implicit motor learning task, we show that reward leads to enhancement of learning in human subjects, whereas punishment is associated only with improvement in motor performance. Furthermore, these behavioral effects have distinct neural substrates with the learning effect of reward being mediated through the dorsal striatum and the performance effect of punishment through the insula. Our results suggest that reward and punishment engage separate motivational systems with distinctive behavioral effects and neural substrates. PMID:19144843

  14. Dual roles of dopamine in food and drug seeking: the drive-reward paradox.

    PubMed

    Wise, Roy A

    2013-05-01

    The question of whether (or to what degree) obesity reflects addiction to high-energy foods often narrows to the question of whether the overeating of these foods causes the same long-term neuroadaptations as are identified with the late stages of addiction. Of equal or perhaps greater interest is the question of whether common brain mechanisms mediate the acquisition and development of eating and drug-taking habits. The earliest evidence on this question is rooted in early studies of brain stimulation reward. Lateral hypothalamic electrical stimulation can be reinforcing in some conditions and can motivate feeding in others. That stimulation of the same brain region should be both reinforcing and drive inducing is paradoxical; why should an animal work to induce a drive-like state such as hunger? This is known as the drive-reward paradox. Insights into the substrates of the drive-reward paradox suggest an answer to the controversial question of whether the dopamine system--a system downstream from the stimulated fibers of the lateral hypothalamus--is more critically involved in wanting or in liking of various rewards including food and addictive drugs. That the same brain circuitry is implicated in the motivation for and the reinforcement by both food and addictive drugs extends the argument for a common mechanism underlying compulsive overeating and compulsive drug taking.

  15. Dopamine genes and reward dependence in adolescents with excessive internet video game play.

    PubMed

    Han, Doug Hyun; Lee, Young Sik; Yang, Kevin C; Kim, Eun Young; Lyoo, In Kyoon; Renshaw, Perry F

    2007-09-01

    Excessive internet video game play (EIGP) has emerged as a leading cause of behavioral and developmental problems in adolescents. Recent research has implicated the role of striatal dopaminergic system in the behavioral maladaptations associated with EIGP. This study investigates the reward-dependence characteristics in EIGP adolescents as it potentially relates to genetic polymorphisms of the dopaminergic system and temperament. Seventy-nine male EIGP adolescents and 75 age- and gender-matched healthy comparison adolescents were recruited. Associations were tested with respect to the reward-dependence (RD) scale in Cloninger's Temperament and Character Inventory and the frequencies of 3 dopamine polymorphisms: Taq1A1 allele of the dopamine D2 receptor (DRD2 Taq1A1) and Val158Met in the Catecholamine-O-Methyltransferase (COMT) genes. The Taq1A1 and low activity (COMT) alleles were significantly more prevalent in the EIGP group relative to the comparison group. The present EIGP group had significantly higher RD scores than controls. Within the EIGP group, the presence of the Taq1A1 allele correlated with higher RD scores. Our findings suggest that EIGP subjects have higher reward dependency and an increased prevalence of the DRD2 Taq1A1 and COMT alleles. In particular, the DRD2 Taq1A1 allele seems to be associated with reward dependence in EIGP adolescents.

  16. Reward Sensitivity Enhances Ventrolateral Prefrontal Cortex Activation during Free Choice

    PubMed Central

    Cho, Catherine; Smith, David V.; Delgado, Mauricio R.

    2016-01-01

    Expressing one's preference via choice can be rewarding, particularly when decisions are voluntarily made as opposed to being forced. An open question is whether engaging in choices involving rewards recruits distinct neural systems as a function of sensitivity to reward. Reward sensitivity is a trait partly influenced by the mesolimbic dopamine system, which can impact an individual's neural and behavioral response to reward cues. Here, we investigated how reward sensitivity contributes to neural activity associated with free and forced choices. Participants underwent a simple decision-making task, which presented free- or forced-choice trials in the scanner. Each trial presented two cues (i.e., points or information) that led to monetary reward at the end of the task. In free-choice trials, participants were offered the opportunity to choose between different reward cues (e.g., points vs. information), whereas forced-choice trials forced individuals to choose within a given reward cue (e.g., information vs. information, or points vs. points). We found enhanced ventrolateral prefrontal cortex (VLPFC) activation during free choice compared to forced choice in individuals with high reward sensitivity scores. Next, using the VLPFC as a seed, we conducted a PPI analysis to identify brain regions that enhance connectivity with the VLPFC during free choice. Our PPI analyses on free vs. forced choice revealed increased VLPFC connectivity with the posterior cingulate and precentral gyrus in reward sensitive individuals. These findings suggest reward sensitivity may recruit attentional control processes during free choice potentially supporting goal-directed behavior and action selection. PMID:27917106

  17. SOME BEHAVIORAL CORRELATES OF BRAIN-STIMULATION REWARD. PART A.

    DTIC Science & Technology

    This work has dealt primarily with some of the behavioral effects of brain - stimulation reward, in contrast with the more usual emphasis on...first lever, free of the side effects of brain stimulation per se,reflect the behavioral reward value of the second chain member. It was found that...The report presents results with regard to those variables and describes findings in experiments designed to make a direct comparison between food and brain - stimulation reward. (Author)

  18. Hypoalgesia Induced by Reward Devaluation in Rats

    PubMed Central

    Jiménez-García, Ana María; Ruíz-Leyva, Leandro; Cendán, Cruz Miguel; Torres, Carmen; Papini, Mauricio R.; Morón, Ignacio

    2016-01-01

    Reduced sensitivity to physical pain (hypoalgesia) has been reported after events involving reward devaluation. Reward devaluation was implemented in a consummatory successive negative contrast (cSNC) task. Food-deprived Wistar rats had access to 32% sucrose during 16 sessions followed by access to 4% sucrose during 3 additional sessions. An unshifted control group had access to 4% sucrose throughout the 19 sessions. Pain sensitivity was measured using von Frey filaments (Experiment 1) and Hargreaves thermal stimuli (Experiment 2) in pretraining baseline, 5 min, and 300 min after either the first (session 17) or second (session 18) devaluation session in the cSNC situation. Sucrose consumption was lower in downshifted groups relative to unshifted groups during postshift sessions—the cSNC effect. Hypoalgesia was observed in downshifted groups relative to unshifted controls when pain sensitivity was assessed 5 min after either the first or second devaluation session, regardless of the pain sensitivity test used. Both pain sensitivity tests yielded evidence of hypoalgesia 300 min after the second downshift session, but not 300 min after the first devaluation session. Whereas hypoalgesia was previously shown only after the second devaluation session, here we report evidence of hypoalgesia after both the first and second devaluation sessions using mechanical and thermal nociceptive stimuli. Moreover, the hypoalgesia observed 300 min after the second devaluation session in both experiments provides unique evidence of the effects of reward loss on sensitivity to physical pain 5 hours after the loss episode. The underlying neurobehavioral mechanisms remain to be identified. PMID:27764142

  19. Working memory load strengthens reward prediction errors.

    PubMed

    Collins, Anne G E; Ciullo, Brittany; Frank, Michael J; Badre, David

    2017-03-20

    Reinforcement learning in simple instrumental tasks is usually modeled as a monolithic process in which reward prediction errors are used to update expected values of choice options. This modeling ignores the different contributions of different memory and decision-making systems thought to contribute even to simple learning. In an fMRI experiment, we asked how working memory and incremental reinforcement learning processes interact to guide human learning. Working memory load was manipulated by varying the number of stimuli to be learned across blocks. Behavioral results and computational modeling confirmed that learning was best explained as a mixture of two mechanisms: a fast, capacity-limited, and delay-sensitive working memory process together with slower reinforcement learning. Model-based analysis of fMRI data showed that striatum and lateral prefrontal cortex were sensitive to reward prediction error, as shown previously, but critically, these signals were reduced when the learning problem was within capacity of working memory. The degree of this neural interaction related to individual differences in the use of working memory to guide behavioral learning. These results indicate that the two systems do not process information independently, but rather interact during learning.SIGNIFICANCE STATEMENTReinforcement learning theory has been remarkably productive at improving our understanding of instrumental learning as well as dopaminergic and striatal network function across many mammalian species. However, this neural network is only one contributor to human learning, and other mechanisms such as prefrontal cortex working memory, also play a key role. Our results show in addition that these other players interact with the dopaminergic RL system, interfering with its key computation of reward predictions errors.

  20. A Typology Framework of Loyalty Reward Programs

    NASA Astrophysics Data System (ADS)

    Cao, Yuheng; Nsakanda, Aaron Luntala; Mann, Inder Jit Singh

    Loyalty reward programs (LRPs), initially developed as marketing programs to enhance customer retention, have now become an important part of customer-focused business strategy. With the proliferation and increasing economy impact of the programs, the management complexity in the programs has also increased. However, despite widespread adoption of LRPs in business, academic research in the field seems to lag behind its practical application. Even the fundamental questions such as what LRPs are and how to classify them have not yet been fully addressed. In this paper, a comprehensive framework for LRP classification is proposed, which provides a foundation for further study of LRP design and planning issues.

  1. Reward Comparison: The Achilles' heel and hope for addiction.

    PubMed

    Grigson, Patricia Sue

    2008-01-01

    In the words of the late Charles Flaherty, reward comparison is commonplace. Rats and man, it appears, compare all rewards and this capacity likely contributes to our ability to select the most appropriate reward/behavior (food, water, salt, sex), at the most ideal level (e.g., a certain sweetness), at any given time. A second advantage of our predisposition for reward comparison is that the availability of rich alternative rewards can protect against our becoming addicted to any single reward/behavior. Thus, the potential protective effects of natural rewards/enrichment are addressed. Despite this, behavior can become inflexible when, through the development of addiction, stress, drug, or cues elicit craving, withdrawal, and ultimately, drug-seeking. Drug-seeking corresponds with a 'window of inopportunity', when even potent natural rewards have little or no impact on behavior. During this time, there is a unitary solution to the need state, and that solution is drug. The present animal model explores this 'window of inopportunity' when natural rewards are devalued and drug-seeking is engaged and considers a mode of possible intervention.

  2. Human ventromedial prefrontal lesions alter incentivisation by reward

    PubMed Central

    Manohar, Sanjay G.; Husain, Masud

    2016-01-01

    Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. PMID:26874940

  3. Reward and cooperation in the spatial public goods game

    NASA Astrophysics Data System (ADS)

    Szolnoki, A.; Perc, M.

    2010-11-01

    The promise of punishment and reward in promoting public cooperation is debatable. While punishment is traditionally considered more successful than reward, the fact that the cost of punishment frequently fails to offset gains from enhanced cooperation has lead some to reconsider reward as the main catalyst behind collaborative efforts. Here we elaborate on the "stick vs. carrot" dilemma by studying the evolution of cooperation in the spatial public goods game, where besides the traditional cooperators and defectors, rewarding cooperators supplement the array of possible strategies. The latter are willing to reward cooperative actions at a personal cost, thus effectively downgrading pure cooperators to second-order free-riders due to their unwillingness to bear these additional costs. Consequently, we find that defection remains viable, especially if the rewarding is costly. Rewards, however, can promote cooperation, especially if the synergetic effects of cooperation are low. Surprisingly, moderate rewards may promote cooperation better than high rewards, which is due to the spontaneous emergence of cyclic dominance between the three strategies.

  4. Measuring Social Motivation Using Signal Detection and Reward Responsiveness

    PubMed Central

    Chevallier, Coralie; Tonge, Natasha; Safra, Lou; Kahn, David; Kohls, Gregor; Miller, Judith; Schultz, Robert T.

    2016-01-01

    Background Recent trends in psychiatry have emphasized the need for a shift from categorical to dimensional approaches. Of critical importance to this transformation is the availability of tools to objectively quantify behaviors dimensionally. The present study focuses on social motivation, a dimension of behavior that is central to a range of psychiatric conditions but for which a particularly small number of assays currently exist. Methods In Study 1 (N = 48), healthy adults completed a monetary reward task and a social reward task, followed by completion of the Chapman Physical and Social Anhedonia Scales. In Study 2 (N = 26), an independent sample was recruited to assess the robustness of Study 1’s findings. Results The reward tasks were analyzed using signal detection theory to quantify how much reward cues bias participants’ responses. In both Study 1 and Study 2, social anhedonia scores were negatively correlated with change in response bias in the social reward task but not in the monetary reward task. A median split on social anhedonia scores confirmed that participants with high social anhedonia showed less change in response bias in the social reward task compared to participants with low social anhedonia. Conclusions This study confirms that social anhedonia selectively affects how much an individual changes their behavior based on the presence of socially rewarding cues and establishes a tool to quantify social reward responsiveness dimensionally. PMID:27907025

  5. Extrinsic rewards undermine altruistic tendencies in 20-month-olds.

    PubMed

    Warneken, Felix; Tomasello, Michael

    2008-11-01

    The current study investigated the influence of rewards on very young children's helping behavior. After 20-month-old infants received a material reward during a treatment phase, they subsequently were less likely to engage in further helping during a test phase as compared with infants who had previously received social praise or no reward at all. This so-called overjustification effect suggests that even the earliest helping behaviors of young children are intrinsically motivated and that socialization practices involving extrinsic rewards can undermine this tendency.

  6. Validation and extension of the reward-mountain model

    PubMed Central

    Breton, Yannick-André; Mullett, Ada; Conover, Kent; Shizgal, Peter

    2013-01-01

    The reward-mountain model relates the vigor of reward seeking to the strength and cost of reward. Application of this model provides information about the stage of processing at which manipulations such as drug administration, lesions, deprivation states, and optogenetic interventions act to alter reward seeking. The model has been updated by incorporation of new information about frequency following in the directly stimulated neurons responsible for brain stimulation reward and about the function that maps objective opportunity costs into subjective ones. The behavioral methods for applying the model have been updated and improved as well. To assess the impact of these changes, two related predictions of the model that were supported by earlier work have been retested: (1) altering the duration of rewarding brain stimulation should change the pulse frequency required to produce a reward of half-maximal intensity, and (2) this manipulation should not change the opportunity cost at which half-maximal performance is directed at earning a maximally intense reward. Prediction 1 was supported in all six subjects, but prediction 2 was supported in only three. The latter finding is interpreted to reflect recruitment, at some stimulation sites, of a heterogeneous reward substrate comprising dual, parallel circuits that integrate the stimulation-induced neural signals. PMID:24098275

  7. Performability analysis using semi-Markov reward processes

    NASA Technical Reports Server (NTRS)

    Ciardo, Gianfranco; Marie, Raymond A.; Sericola, Bruno; Trivedi, Kishor S.

    1990-01-01

    Beaudry (1978) proposed a simple method of computing the distribution of performability in a Markov reward process. Two extensions of Beaudry's approach are presented. The method is generalized to a semi-Markov reward process by removing the restriction requiring the association of zero reward to absorbing states only. The algorithm proceeds by replacing zero-reward nonabsorbing states by a probabilistic switch; it is therefore related to the elimination of vanishing states from the reachability graph of a generalized stochastic Petri net and to the elimination of fast transient states in a decomposition approach to stiff Markov chains. The use of the approach is illustrated with three applications.

  8. Dopamine neurons learn relative chosen value from probabilistic rewards

    PubMed Central

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

    2016-01-01

    Economic theories posit reward probability as one of the factors defining reward value. Individuals learn the value of cues that predict probabilistic rewards from experienced reward frequencies. Building on the notion that responses of dopamine neurons increase with reward probability and expected value, we asked how dopamine neurons in monkeys acquire this value signal that may represent an economic decision variable. We found in a Pavlovian learning task that reward probability-dependent value signals arose from experienced reward frequencies. We then assessed neuronal response acquisition during choices among probabilistic rewards. Here, dopamine responses became sensitive to the value of both chosen and unchosen options. Both experiments showed also the novelty responses of dopamine neurones that decreased as learning advanced. These results show that dopamine neurons acquire predictive value signals from the frequency of experienced rewards. This flexible and fast signal reflects a specific decision variable and could update neuronal decision mechanisms. DOI: http://dx.doi.org/10.7554/eLife.18044.001 PMID:27787196

  9. Framing Reinforcement Learning from Human Reward: Reward Positivity, Temporal Discounting, Episodicity, and Performance

    DTIC Science & Technology

    2014-09-29

    Achieving master level play in 9× 9 computer go. In: Proceedings of AAAI. pp. 1537–1540. Grollman, D., Jenkins, O., Apr 2007. Dogged learning for robots...punishment and will make the screen flash red. You can think of this as similar to training a dog or another animal through reward and punishment, but it will

  10. Quality Reward and Awards: Quality Has Its Own Reward, but an Award Helps Speed the Process.

    ERIC Educational Resources Information Center

    Penniman, W. David

    1993-01-01

    Advocates the use of the Total Quality Management (TQM) model for libraries to survive financially and to retain their customers. An award for library quality based on the Malcolm Baldridge Award is proposed to enable institutions to use an evaluation procedure that rewards a commitment to continuous improvement. (Contains five references.) (EAM)

  11. Reward expectancy promotes generalized increases in attentional bias for rewarding stimuli.

    PubMed

    Jones, Andrew; Hogarth, Lee; Christiansen, Paul; Rose, Abigail K; Martinovic, Jasna; Field, Matt

    2012-01-01

    Expectations of drug availability increase the magnitude of attentional biases for drug-related cues. However, it is unknown whether these effects are outcome specific, or whether expectation of a specific reinforcer produces a general enhancement of attentional bias for other types of rewarding cues. In the present study, 31 social drinkers completed an eye-tracking task in which attentional bias for alcohol- and chocolate-related cues was assessed while the expectation of receiving alcohol and chocolate was manipulated on a trial-by-trial basis. Participants showed attentional bias for alcohol and chocolate cues (relative to neutral cues) overall. Importantly, these attentional biases for reward cues were magnified when participants expected to receive alcohol and chocolate, but effects were not outcome specific: The expectation of receiving either alcohol or chocolate increased attentional bias for both alcohol and chocolate cues. Results suggest that anticipation of reward produces a general rather than an outcome-specific enhancement of attentional bias for reward-related stimuli.

  12. Cannabinoids reward sensitivity in a neurodevelopmental animal model of schizophrenia: a brain stimulation reward study.

    PubMed

    Gallo, Alexandra; Bouchard, Claude; Fortier, Emmanuel; Ducrot, Charles; Rompré, Pierre-Paul

    2014-09-01

    The comorbidity schizophrenia and cannabis has a high prevalence. The consumption of cannabis is ten times higher among schizophrenia patients, suggesting that these patients could be differentially sensitive to its motivational effects. To study this question, we investigated the motivational effects of cannabinoid agonists using the brain stimulation reward paradigm and a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). Using the curve-shift paradigm, we first compared the effect single dose (0.75mg/kg) of amphetamine in sham and NVHL rats on reward and operant responding. Then, in different groups of NVHL and sham rats, we studied the effect of delta-9-tetrahydrocannabinnol (THC, 0.5mg/kg, i.p.) and WIN55,212-2 (WIN, 1 and 3mg/kg, i.p.) Rats were initially trained to self-administer an electrical stimulation to the posterio-medial mesencephalon. Once responding was stable, reward threshold defined as the frequency required to induce a half maximum response rate was measured before and after injection of the drug or the vehicle. Results show that amphetamine enhanced reward in sham and NVHL rats, an effect that was shorter in duration in NVHL rats. THC produced a weak attenuation of reward in sham rats while WIN produced a dose-dependent attenuation in NVHL; the attenuation effect of WIN was blocked by the cannabinoid antagonist, AM251. WIN also produced an attenuation of performance in sham and NVHL rats, and this effect was partially prevented by AM251. These results provide the additional evidence that the motivational effect of cannabinoids is altered in animals with a schizophrenia-like phenotype.

  13. Inferring reward prediction errors in patients with schizophrenia: a dynamic reward task for reinforcement learning

    PubMed Central

    Li, Chia-Tzu; Lai, Wen-Sung; Liu, Chih-Min; Hsu, Yung-Fong

    2014-01-01

    Abnormalities in the dopamine system have long been implicated in explanations of reinforcement learning and psychosis. The updated reward prediction error (RPE)—a discrepancy between the predicted and actual rewards—is thought to be encoded by dopaminergic neurons. Dysregulation of dopamine systems could alter the appraisal of stimuli and eventually lead to schizophrenia. Accordingly, the measurement of RPE provides a potential behavioral index for the evaluation of brain dopamine activity and psychotic symptoms. Here, we assess two features potentially crucial to the RPE process, namely belief formation and belief perseveration, via a probability learning task and reinforcement-learning modeling. Forty-five patients with schizophrenia [26 high-psychosis and 19 low-psychosis, based on their p1 and p3 scores in the positive-symptom subscales of the Positive and Negative Syndrome Scale (PANSS)] and 24 controls were tested in a feedback-based dynamic reward task for their RPE-related decision making. While task scores across the three groups were similar, matching law analysis revealed that the reward sensitivities of both psychosis groups were lower than that of controls. Trial-by-trial data were further fit with a reinforcement learning model using the Bayesian estimation approach. Model fitting results indicated that both psychosis groups tend to update their reward values more rapidly than controls. Moreover, among the three groups, high-psychosis patients had the lowest degree of choice perseveration. Lumping patients' data together, we also found that patients' perseveration appears to be negatively correlated (p = 0.09, trending toward significance) with their PANSS p1 + p3 scores. Our method provides an alternative for investigating reward-related learning and decision making in basic and clinical settings. PMID:25426091

  14. Blockade of melanocortin transmission inhibits cocaine reward

    PubMed Central

    Hsu, Richard; Taylor, Jane R.; Newton, Samuel S.; Alvaro, John D.; Haile, Colin; Han, G.; Hruby, Victor J.; Nestler, Eric J.; Duman, Ronald S.

    2009-01-01

    Abstract Melanocortins and the melanocortin-4 receptor (MC4-R) are enriched in the nucleus accumbens, a brain region that has been implicated in the rewarding action of cocaine and other drugs of abuse. In the present study we use a number of rat behavioral models to show that infusion of a melanocortin peptide antagonist into the nucleus accumbens blocks the reinforcing, incentive motivational, and locomotor sensitizing effects of cocaine. We also show that locomotor responses to repeated cocaine exposure are completely blocked in MC4-R null mutant mice and reduced in Agouti mice that overexpress an endogenous inhibitor of melanocortins in the brain. The results also demonstrate that cocaine administration increases the expression of MC4-R in the nucleus accumbens and striatum, and that MC4-R is co-localized with prodynorphin in medium spiny neurons in the nucleus accumbens. Together, these findings indicate that the behavioral actions of cocaine are dependent on activation of MC4-R, and suggest that upregulation of this receptor by drug exposure may contribute to sensitization of these behavioral responses. Modulation of cocaine reward is a novel action of the melanocortin–MC4-R system and could be targeted for the development of new medications for cocaine addiction. PMID:15869520

  15. Abnormal reward functioning across substance use disorders and major depressive disorder: Considering reward as a transdiagnostic mechanism.

    PubMed

    Baskin-Sommers, Arielle R; Foti, Dan

    2015-11-01

    A common criticism of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) is that its criteria are based more on behavioral descriptions than on underlying biological mechanisms. Increasingly, calls have intensified for a more biologically-based approach to conceptualizing, studying, and treating psychological disorders, as exemplified by the Research Domain Criteria Project (RDoC). Among the most well-studied neurobiological mechanisms is reward processing. Moreover, individual differences in reward sensitivity are related to risk for substance abuse and depression. The current review synthesizes the available preclinical, electrophysiological, and neuroimaging literature on reward processing from a transdiagnostic, multidimensional perspective. Findings are organized with respect to key reward constructs within the Positive Valence Systems domain of the RDoC matrix, including initial responsiveness to reward (physiological 'liking'), approach motivation (physiological 'wanting'), and reward learning/habit formation. In the current review, we (a) describe the neural basis of reward, (b) elucidate differences in reward activity in substance abuse and depression, and (c) suggest a framework for integrating these disparate literatures and discuss the utility of shifting focus from diagnosis to process for understanding liability and co-morbidity. Ultimately, we believe that an integrative focus on abnormal reward functioning across the full continuum of clinically heterogeneous samples, rather than within circumscribed diagnostic categories, might actually help to refine the phenotypes and improve the prediction of onset and recovery of these disorders.

  16. Autistic traits modulate mimicry of social but not nonsocial rewards.

    PubMed

    Haffey, Anthony; Press, Clare; O'Connell, Garret; Chakrabarti, Bhismadev

    2013-12-01

    Autism Spectrum Conditions (ASC) are associated with diminished responsiveness to social stimuli, and especially to social rewards such as smiles. Atypical responsiveness to social rewards, which reinforce socially appropriate behavior in children, can potentially lead to a cascade of deficits in social behavior. Individuals with ASC often show diminished spontaneous mimicry of social stimuli in a natural setting. In the general population, mimicry is modulated both by the reward value and the sociality of the stimulus (i.e., whether the stimulus is perceived to belong to a conspecific or an inanimate object). Since empathy and autistic traits are distributed continuously in the general population, this study aimed to test if and how these traits modulated automatic mimicry of rewarded social and nonsocial stimuli. High and low rewards were associated with human and robot hands using a conditioned learning paradigm. Thirty-six participants from the general population then completed a mimicry task involving performing a prespecified hand movement which was either compatible or incompatible with a hand movement presented to the participant. High autistic traits (measured using the Autism Spectrum Quotient, AQ) predicted lesser mimicry of high-reward than low-reward conditioned human hands, whereas trait empathy showed an opposite pattern of correlations. No such relations were observed for high-reward vs. low-reward conditioned robot hands. These results demonstrate how autistic traits and empathy modulate the effects of reward on mimicry of social compared to nonsocial stimuli. This evidence suggests a potential role for the reward system in underlying the atypical social behavior in individuals with ASC, who constitute the extreme end of the spectrum of autistic traits.

  17. Honeybees learn the sign and magnitude of reward variations.

    PubMed

    Gil, Mariana; De Marco, Rodrigo J

    2009-09-01

    In this study, we asked whether honeybees learn the sign and magnitude of variations in the level of reward. We designed an experiment in which bees first had to forage on a three-flower patch offering variable reward levels, and then search for food at the site in the absence of reward and after a long foraging pause. At the time of training, we presented the bees with a decrease in reward level or, instead, with either a small or a large increase in reward level. Testing took place as soon as they visited the patch on the day following training, when we measured the bees' food-searching behaviours. We found that the bees that had experienced increasing reward levels searched for food more persistently than the bees that had experienced decreasing reward levels, and that the bees that had experienced a large increase in reward level searched for food more persistently than the bees that had experienced a small increase in reward level. Because these differences at the time of testing cannot be accounted for by the bees' previous crop loads and food-intake rates, our results unambiguously demonstrate that honeybees adjust their investment of time/energy during foraging in relation to both the sign and the magnitude of past variations in the level of reward. It is likely that such variations lead to the formation of reward expectations enhancing a forager's reliance on a feeding site. Ultimately, this would make it more likely for honeybees to find food when forage is scarce.

  18. Neuroethics of deep brain stimulation for mental disorders: brain stimulation reward in humans.

    PubMed

    Oshima, Hideki; Katayama, Yoichi

    2010-01-01

    The theoretical basis of some deep brain stimulation (DBS) trials undertaken in the early years was the phenomenon of "brain stimulation reward (BSR)," which was first identified in rats. The animals appeared to be rewarded by pleasure caused by the stimulation of certain brain regions (reward system), such as the septal area. "Self-stimulation" experiments, in which rats were allowed to stimulate their own brain by pressing a freely accessible lever, they quickly learned lever pressing and sometimes continued to stimulate until they exhausted themselves. BSR was also observed with DBS of the septal area in humans. DBS trials in later years were undertaken on other theoretical bases, but unexpected BSR was sometimes induced by stimulation of some areas, such as the locus coeruleus complex. When BSR was induced, the subjects experienced feelings that were described as "cheerful," "alert," "good," "well-being," "comfort," "relaxation," "joy," or "satisfaction." Since the DBS procedure is equivalent to a "self-stimulation" experiment, they could become "addicted to the stimulation itself" or "compulsive about the stimulation," and stimulate themselves "for the entire day," "at maximum amplitude" and, in some instances, "into convulsions." DBS of the reward system has recently been applied to alleviate anhedonia in patients with refractory major depression. Although this approach appears promising, there remains a difficult problem: who can adjust their feelings and reward-oriented behavior within the normal range? With a self-stimulation procedure, the BSR may become uncontrollable. To develop DBS to the level of a standard therapy for mental disorders, we need to discuss "Who has the right to control the mental condition?" and "Who makes decisions" on "How much control is appropriate?" in daily life.

  19. Slave to habit? Obesity is associated with decreased behavioural sensitivity to reward devaluation.

    PubMed

    Horstmann, Annette; Dietrich, Anja; Mathar, David; Pössel, Maria; Villringer, Arno; Neumann, Jane

    2015-04-01

    The motivational value of food is lower during satiety compared to fasting. Dynamic changes in motivational value promote food seeking or meal cessation. In obesity this mechanism might be compromised since obese subjects ingest energy beyond homeostatic needs. Thus, lower adaptation of eating behaviour with respect to changes in motivational value might cause food overconsumption in obesity. To test this hypothesis, we implemented a selective satiation procedure to investigate the relationship between obesity and the size of the behavioural devaluation effect in humans. Lean to obese men (mean age 25.9, range 19-30 years; mean BMI 29.1, range 19.2-45.1 kg/m(2)) were trained on a free operant paradigm and learned to associate cues with the possibility to win different food rewards by pressing a button. After the initial training phase, one of the rewards was devalued by consumption. Response rates for and wanting of the different rewards were measured pre and post devaluation. Behavioural sensitivity to reward devaluation, measured as the magnitude of difference between pre and post responses, was regressed against BMI. Results indicate that (1) higher BMI compared to lower BMI in men led to an attenuated behavioural adjustment to reward devaluation, and (2) the decrease in motivational value was associated with the decrease in response rate between pre and post. Change in explicitly reported motivational value, however, was not affected by BMI. Thus, we conclude that high BMI in men is associated with lower behavioural adaptation with respect to changes in motivational value of food, possibly resulting in automatic overeating patterns that are hard to control in daily life.

  20. Dopamine Replacement Therapy, Learning and Reward Prediction in Parkinson’s Disease: Implications for Rehabilitation

    PubMed Central

    Ferrazzoli, Davide; Carter, Adrian; Ustun, Fatma S.; Palamara, Grazia; Ortelli, Paola; Maestri, Roberto; Yücel, Murat; Frazzitta, Giuseppe

    2016-01-01

    The principal feature of Parkinson’s disease (PD) is the impaired ability to acquire and express habitual-automatic actions due to the loss of dopamine in the dorsolateral striatum, the region of the basal ganglia associated with the control of habitual behavior. Dopamine replacement therapy (DRT) compensates for the lack of dopamine, representing the standard treatment for different motor symptoms of PD (such as rigidity, bradykinesia and resting tremor). On the other hand, rehabilitation treatments, exploiting the use of cognitive strategies, feedbacks and external cues, permit to “learn to bypass” the defective basal ganglia (using the dorsolateral area of the prefrontal cortex) allowing the patients to perform correct movements under executive-volitional control. Therefore, DRT and rehabilitation seem to be two complementary and synergistic approaches. Learning and reward are central in rehabilitation: both of these mechanisms are the basis for the success of any rehabilitative treatment. Anyway, it is known that “learning resources” and reward could be negatively influenced from dopaminergic drugs. Furthermore, DRT causes different well-known complications: among these, dyskinesias, motor fluctuations, and dopamine dysregulation syndrome (DDS) are intimately linked with the alteration in the learning and reward mechanisms and could impact seriously on the rehabilitative outcomes. These considerations highlight the need for careful titration of DRT to produce the desired improvement in motor symptoms while minimizing the associated detrimental effects. This is important in order to maximize the motor re-learning based on repetition, reward and practice during rehabilitation. In this scenario, we review the knowledge concerning the interactions between DRT, learning and reward, examine the most impactful DRT side effects and provide suggestions for optimizing rehabilitation in PD. PMID:27378872

  1. Racial Differences in the Value of Job Rewards

    ERIC Educational Resources Information Center

    Shapiro, E. Gary

    1977-01-01

    Black workers were found more likely than white workers to prefer extrinsic rewards of high income and job security and less likely to prefer an intrinsic reward of feelings of job accomplishment. These Findings are discussed as they bear on the race class issue and Maslow's theory of job values. (Author/GC)

  2. RESPONSE TO VARYING LEVELS OF CONDITIONING REWARDS. FINAL REPORT.

    ERIC Educational Resources Information Center

    SILVERMAN, ROBERT E.; AND OTHERS

    TWO EXPERIMENTS WERE CONDUCTED TO CLASSIFY AND TO CONDITION REWARD RESPONSIVENESS IN KINDERGARTEN CHILDREN. IN THE FIRST EXPERIMENT, 207 CHILDREN WITH A MEDIAN AGE OF 6.0 WERE CLASSIFIED ACCORDING TO THEIR RESPONSIVENESS TO A HIERARCHY OF REWARDS. AFTER TWO SESSIONS INVOLVING TWO-CHOICE INSTRUMENTAL CONDITIONING TASKS, 60 PERCENT OF THE CHILDREN…

  3. Trait Anticipatory Pleasure Predicts Effort Expenditure for Reward

    PubMed Central

    Geaney, Joachim T.; Treadway, Michael T.; Smillie, Luke D.

    2015-01-01

    Research in motivation and emotion has been increasingly influenced by the perspective that processes underpinning the motivated approach of rewarding goals are distinct from those underpinning enjoyment during reward consummation. This distinction recently inspired the construction of the Temporal Experience of Pleasure Scale (TEPS), a self-report measure that distinguishes trait anticipatory pleasure (pre-reward feelings of desire) from consummatory pleasure (feelings of enjoyment and gratification upon reward attainment). In a university community sample (N = 97), we examined the TEPS subscales as predictors of (1) the willingness to expend effort for monetary rewards, and (2) affective responses to a pleasant mood induction procedure. Results showed that both anticipatory pleasure and a well-known trait measure of reward motivation predicted effort-expenditure for rewards when the probability of being rewarded was relatively low. Against expectations, consummatory pleasure was unrelated to induced pleasant affect. Taken together, our findings provide support for the validity of the TEPS anticipatory pleasure scale, but not the consummatory pleasure scale. PMID:26115223

  4. Antisocial pool rewarding does not deter public cooperation

    PubMed Central

    Szolnoki, Attila; Perc, Matjaž

    2015-01-01

    Rewarding cooperation is in many ways expected behaviour from social players. However, strategies that promote antisocial behaviour are also surprisingly common, not just in human societies, but also among eusocial insects and bacteria. Examples include sanctioning of individuals who behave prosocially, or rewarding of free-riders who do not contribute to collective enterprises. We therefore study the public goods game with antisocial and prosocial pool rewarding in order to determine the potential negative consequences on the effectiveness of positive incentives to promote cooperation. Contrary to a naive expectation, we show that the ability of defectors to distribute rewards to their like does not deter public cooperation as long as cooperators are able to do the same. Even in the presence of antisocial rewarding, the spatial selection for cooperation in evolutionary social dilemmas is enhanced. Since the administration of rewards to either strategy requires a considerable degree of aggregation, cooperators can enjoy the benefits of their prosocial contributions as well as the corresponding rewards. Defectors when aggregated, on the other hand, can enjoy antisocial rewards, but due to their lack of contributions to the public good they ultimately succumb to their inherent inability to secure a sustainable future. Strategies that facilitate the aggregation of akin players, even if they seek to promote antisocial behaviour, thus always enhance the long-term benefits of cooperation. PMID:26400746

  5. Managing Reward in Developing Economies: The Challenge for Multinational Corporations

    ERIC Educational Resources Information Center

    Opute, John

    2010-01-01

    Reward has been, and continues to be, subject to significant changes in developing economies; the industrial relations model prevalent being driven by the complex socio-economic and cultural paradigms and the increasing demands of globalisation. The issue of reward in developing economies is therefore central and dependent on numerous contextual…

  6. Reward association facilitates distractor suppression in human visual search.

    PubMed

    Gong, Mengyuan; Yang, Feitong; Li, Sheng

    2016-04-01

    Although valuable objects are attractive in nature, people often encounter situations where they would prefer to avoid such distraction while focusing on the task goal. Contrary to the typical effect of attentional capture by a reward-associated item, we provide evidence for a facilitation effect derived from the active suppression of a high reward-associated stimulus when cuing its identity as distractor before the display of search arrays. Selection of the target is shown to be significantly faster when the distractors were in high reward-associated colour than those in low reward-associated or non-rewarded colours. This behavioural reward effect was associated with two neural signatures before the onset of the search display: the increased frontal theta oscillation and the strengthened top-down modulation from frontal to anterior temporal regions. The former suggests an enhanced working memory representation for the reward-associated stimulus and the increased need for cognitive control to override Pavlovian bias, whereas the latter indicates that the boost of inhibitory control is realized through a frontal top-down mechanism. These results suggest a mechanism in which the enhanced working memory representation of a reward-associated feature is integrated with task demands to modify attentional priority during active distractor suppression and benefit behavioural performance.

  7. Dissociating motivation from reward in human striatal activity.

    PubMed

    Miller, Eric M; Shankar, Maya U; Knutson, Brian; McClure, Samuel M

    2014-05-01

    Neural activity in the striatum has consistently been shown to scale with the value of anticipated rewards. As a result, it is common across a number of neuroscientific subdiscliplines to associate activation in the striatum with anticipation of a rewarding outcome or a positive emotional state. However, most studies have failed to dissociate expected value from the motivation associated with seeking a reward. Although motivation generally scales positively with increases in potential reward, there are circumstances in which this linkage does not apply. The current study dissociates value-related activation from that induced by motivation alone by employing a task in which motivation increased as anticipated reward decreased. This design reverses the typical relationship between motivation and reward, allowing us to differentially investigate fMRI BOLD responses that scale with each. We report that activity scaled differently with value and motivation across the striatum. Specifically, responses in the caudate and putamen increased with motivation, whereas nucleus accumbens activity increased with expected reward. Consistent with this, self-report ratings indicated a positive association between caudate and putamen activity and arousal, whereas activity in the nucleus accumbens was more associated with liking. We conclude that there exist regional limits on inferring reward expectation from striatal activation.

  8. The Environmental Reward Observation Scale (EROS): Development, Validity, and Reliability

    ERIC Educational Resources Information Center

    Armento, Maria E. A.; Hopko, Derek R.

    2007-01-01

    Researchers acknowledge a strong association between the frequency and duration of environmental reward and affective mood states, particularly in relation to the etiology, assessment, and treatment of depression. Given behavioral theories that outline environmental reward as a strong mediator of affect and the unavailability of an efficient,…

  9. The Use of Rewards and Punishment in Early Childhood Classrooms

    ERIC Educational Resources Information Center

    Moberly, Deborah A.; Waddle, Jerry L.; Duff, R. Eleanor

    2005-01-01

    Much has been written about the problems associated with reliance on extrinsic rewards and punishment in controlling behavior and motivating students. This study explores the use of extrinsic rewards and punishment by prekindergarten-grade 3 teachers in Missouri. The purpose of the study was to (a) determine the most common motivational practices…

  10. Fear Conditioning Effects on Sensitivity to Drug Reward

    DTIC Science & Technology

    2010-06-01

    morphine . Conditioned drug reward is a relevant model in addiction because environmental cues (e.g. a barroom) induce craving and persistent... morphine . Synaptic plasticity is found in these neural fear and reward circuits and thus drugs which enhance plasticity like histone deacetylase...commercially available drug (sodium butyrate) with high translational utility for human studies. Morphine place conditioning: To measure effects of opiate

  11. Antisocial pool rewarding does not deter public cooperation.

    PubMed

    Szolnoki, Attila; Perc, Matjaž

    2015-10-07

    Rewarding cooperation is in many ways expected behaviour from social players. However, strategies that promote antisocial behaviour are also surprisingly common, not just in human societies, but also among eusocial insects and bacteria. Examples include sanctioning of individuals who behave prosocially, or rewarding of free-riders who do not contribute to collective enterprises. We therefore study the public goods game with antisocial and prosocial pool rewarding in order to determine the potential negative consequences on the effectiveness of positive incentives to promote cooperation. Contrary to a naive expectation, we show that the ability of defectors to distribute rewards to their like does not deter public cooperation as long as cooperators are able to do the same. Even in the presence of antisocial rewarding, the spatial selection for cooperation in evolutionary social dilemmas is enhanced. Since the administration of rewards to either strategy requires a considerable degree of aggregation, cooperators can enjoy the benefits of their prosocial contributions as well as the corresponding rewards. Defectors when aggregated, on the other hand, can enjoy antisocial rewards, but due to their lack of contributions to the public good they ultimately succumb to their inherent inability to secure a sustainable future. Strategies that facilitate the aggregation of akin players, even if they seek to promote antisocial behaviour, thus always enhance the long-term benefits of cooperation.

  12. Reward Retroactively Enhances Memory Consolidation for Related Items

    ERIC Educational Resources Information Center

    Patil, Anuya; Murty, Vishnu P.; Dunsmoor, Joseph E.; Phelps, Elizabeth A.; Davachi, Lila

    2017-01-01

    Reward motivation has been shown to modulate episodic memory processes in order to support future adaptive behavior. However, for a memory system to be truly adaptive, it should enhance memory for rewarded events as well as for neutral events that may seem inconsequential at the time of encoding but can gain importance later. Here, we investigated…

  13. Effects of Teacher Rewards on Recognition and Job Enrichment.

    ERIC Educational Resources Information Center

    Frase, Larry E.

    1989-01-01

    Implications of Herzberg's motivation-hygiene theory for teacher reward programs were tested by comparing changes in teachers' (N=38) job-enrichment opportunities and recognition after the teachers had chosen one of two rewards (travel to professional training conferences or cash). Results were consistent with the motivation-hygiene theory. (IAH)

  14. Recruiter-Applicant Differences in Perceptions of Extrinsic Rewards.

    ERIC Educational Resources Information Center

    David, Kermit R., Jr.; And Others

    1991-01-01

    Examined how accurate recruiters would be in estimating relative preferences of college seniors for important category of extrinsic rewards. Compared preferences of 602 graduating college seniors for 11 extrinsic rewards with preference estimates of 486 recruiters. Recruiters underestimated importance of medical and life insurance, pension plans,…

  15. Extrinsic Rewards Are Education's Past, Not Its Future.

    ERIC Educational Resources Information Center

    Schaps, Eric; Lewis, Catherine

    1991-01-01

    Robert Slavin's position--that extrinsic rewards promote student motivation and learning--may be valid within the context of a "facts-and-skills" curriculum. However, extrinsic rewards are unnecessary when schools offer engaging learning activities; programs addressing social, ethical, and cognitive development; and a supportive…

  16. Rewards for Reading: Their Effects on Reading Motivation

    ERIC Educational Resources Information Center

    Chen, Pin-Hwa; Wu, Jen-Rung

    2010-01-01

    In recent years, many Taiwanese elementary schools have implemented extensive reading activities in their respective campuses. In order to motivate pupils to read, teachers and parents would offer pupils contingent rewards. As we know, the use of rewards in educational settings as a way to improve motivation is a controversial issue. Previous…

  17. When Rewards Go Wrong: A Tale of Five Motivational Misdirects

    ERIC Educational Resources Information Center

    Steel, Piers; MacDonnell, Rhiannon

    2012-01-01

    At the heart of most performance management systems is a reward program. However, even when we are doing everything else right, rewards can go wrong. Here, we explore five ways that external incentives can damage performance, from destroying altruistic behavior to distracting people from the task. Fortunately, most of these downfalls are…

  18. The Effects of Extrinsic Rewards on Admissions Counselors' Performance

    ERIC Educational Resources Information Center

    Gardner-Engel, Miriam

    2010-01-01

    This study examines the best ways to motivate college admissions counselors. A review of literature revealed multiple perspectives on intrinsic and extrinsic as well as tangible and intangible rewards. Primary research was designed to examine the impact of tangible rewards and verbal reinforcements with a convenience sample of nine college…

  19. Behavioral Management of Exceptional Children Using Video Games as Reward.

    ERIC Educational Resources Information Center

    Buckalew, L.W.; Buckalew, Patricia Bowman

    1983-01-01

    Seventeen children ranging in age from 9 to 15 years and from grades four and eight in five classes for students with emotional conflicts were placed on a video game reward system. The observation of enhanced classroom decorum and individual performance of students suggest the effectiveness of this reward in modifying behavior. (Author/PN)

  20. Multi Agent Reward Analysis for Learning in Noisy Domains

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan; Agogino, Adrian K.

    2005-01-01

    In many multi agent learning problems, it is difficult to determine, a priori, the agent reward structure that will lead to good performance. This problem is particularly pronounced in continuous, noisy domains ill-suited to simple table backup schemes commonly used in TD(lambda)/Q-learning. In this paper, we present a new reward evaluation method that allows the tradeoff between coordination among the agents and the difficulty of the learning problem each agent faces to be visualized. This method is independent of the learning algorithm and is only a function of the problem domain and the agents reward structure. We then use this reward efficiency visualization method to determine an effective reward without performing extensive simulations. We test this method in both a static and a dynamic multi-rover learning domain where the agents have continuous state spaces and where their actions are noisy (e.g., the agents movement decisions are not always carried out properly). Our results show that in the more difficult dynamic domain, the reward efficiency visualization method provides a two order of magnitude speedup in selecting a good reward. Most importantly it allows one to quickly create and verify rewards tailored to the observational limitations of the domain.

  1. Neural correlates of reward and attention in macaque area LIP.

    PubMed

    Bendiksby, Michael S; Platt, Michael L

    2006-01-01

    Saccade reaction times decrease and the frequency of target choices increases with the size of rewards delivered for orienting to a particular visual target. Similarly, increasing rewards for orienting to a visual target enhances neuronal responses in the macaque lateral intraparietal area (LIP), as well as other brain areas. These observations raise several questions. First, are reward-related modulations in neuronal activity in LIP, as well as other areas, spatially specific or more global in nature? Second, to what extent does reward modulation of neuronal activity in area LIP reflect changes in visual rather than motor processing? And third, to what degree are reward-related modulations in LIP activity independent of performance-related modulations thought to reflect changes in attention? Here we show that increasing the size of fluid rewards in blocks reduced saccade reaction times and improved performance in monkeys performing a peripherally-cued saccade task. LIP neurons responded to visual cues spatially segregated from the saccade target, and for many neurons visual responses were systematically modulated by expected reward size. Neuronal responses also were positively correlated with reaction times independent of reward size, consistent with re-orienting of attention to the saccade target. These observations suggest that motivation and attention independently contribute to the strength of sustained visual responses in LIP. Our data thus implicate LIP in the integration of the sensory, motor, and motivational variables that guide orienting.

  2. The Use of Different Rules to Allocate Reward and Punishment.

    ERIC Educational Resources Information Center

    Mueller, Charles W.

    Much research has been conducted about how and when individuals allocate rewards, yet little research exists concerning the allocation of punishment. The process of allocating negative outcomes may be different from the decision making process for positive outcomes. To examine the decision making process for allocating rewards and punishment,…

  3. U.S. Geological Survey Rewarding Environment Culture Study, 2002

    USGS Publications Warehouse

    Nash, Janis C.; Paradise-Tornow, Carol A.; Gray, Vicki K.; Griffin-Bemis, Sarah P.; Agnew, Pamela R.; Bouchet, Nicole M.

    2010-01-01

    In its 2001 review of the U.S. Geological Survey (USGS), the National Research Council (NRC, p. 126) cautioned that ?high-quality personnel are essential for developing high-quality science information? and urged the USGS to ?devote substantial efforts to recruiting and retaining excellent staff.? Recognizing the importance of the NRC recommendation, the USGS has committed time and resources to create a rewarding work environment with the goal of achieving the following valued outcomes: ? USGS science vitality ? Customer satisfaction with USGS products and services ? Employee perceptions of the USGS as a rewarding place to work ? Heightened employee morale and commitment ? The ability to recruit and retain employees with critical skills To determine whether this investment of time and resources was proving to be successful, the USGS Human Resources Office conducted a Rewarding Environment Culture Study to answer the following four questions. ? Question 1: Does a rewarding work environment lead to the valued outcomes (identified above) that the USGS is seeking? ? Question 2: Which management, supervisory, and leadership behaviors contribute most to creating a rewarding work environment and to achieving the valued outcomes that the USGS is seeking? ? Question 3: Do USGS employees perceive that the USGS is a rewarding place to work? ? Question 4: What actions can and should be taken to enhance the USGS work environment? To begin the study, a conceptual model of a rewarding USGS environment was developed to test assumptions about a rewarding work environment. The Rewarding Environment model identifies the key components that are thought to contribute to a rewarding work environment and the valued outcomes that are thought to result from having a rewarding work environment. The 2002 Organizational Assessment Survey (OAS) was used as the primary data source for the study because it provided the most readily available data. Additional survey data were included as they

  4. Anhedonia and the brain reward circuitry in depression

    PubMed Central

    Heshmati, Mitra; Russo, Scott J.

    2015-01-01

    Anhedonia, or the loss of pleasure in previously rewarding stimuli, is a core symptom of major depressive disorder that may reflect an underlying dysregulation in reward processing. The mesolimbic dopamine circuit, also known as the brain’s reward circuit, is integral to processing the rewarding salience of stimuli to guide actions. Manifestation of anhedonia and associated depression symptoms like feelings of sadness, changes in appetite, and psychomotor effects, may reflect changes in the brain reward circuitry as a common underlying disease process. This review will synthesize the recent literature from human and rodent studies providing a circuit-level framework for understanding anhedonia in depression, with emphasis on the nucleus accumbens. PMID:26525751

  5. Reward and motivation in pain and pain relief

    PubMed Central

    Navratilova, Edita; Porreca, Frank

    2015-01-01

    Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain. PMID:25254980

  6. Exit, Punishment and Rewards in Commons Dilemmas: An Experimental Study

    PubMed Central

    Bravo, Giangiacomo; Squazzoni, Flaminio

    2013-01-01

    Commons dilemmas are interaction situations where a common good is provided or exploited by a group of individuals so that optimal collective outcomes clash with private interests. Although in these situations, social norms and institutions exist that might help individuals to cooperate, little is known about the interaction effects between positive and negative incentives and exit options by individuals. We performed a modified public good game experiment to examine the effect of exit, rewards and punishment, as well as the interplay between exit and rewards and punishment. We found that punishment had a stronger effect than rewards on cooperation if considered by itself, whereas rewards had a stronger effect when combined with voluntary participation. This can be explained in terms of the ‘framing effect’, i.e., as the combination of exit and rewards might induce people to attach higher expected payoffs to cooperative strategies and expect better behaviour from others. PMID:23936356

  7. Reward and motivation in pain and pain relief.

    PubMed

    Navratilova, Edita; Porreca, Frank

    2014-10-01

    Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain.

  8. Natural rewards, neuroplasticity, and non-drug addictions.

    PubMed

    Olsen, Christopher M

    2011-12-01

    There is a high degree of overlap between brain regions involved in processing natural rewards and drugs of abuse. "Non-drug" or "behavioral" addictions have become increasingly documented in the clinic, and pathologies include compulsive activities such as shopping, eating, exercising, sexual behavior, and gambling. Like drug addiction, non-drug addictions manifest in symptoms including craving, impaired control over the behavior, tolerance, withdrawal, and high rates of relapse. These alterations in behavior suggest that plasticity may be occurring in brain regions associated with drug addiction. In this review, I summarize data demonstrating that exposure to non-drug rewards can alter neural plasticity in regions of the brain that are affected by drugs of abuse. Research suggests that there are several similarities between neuroplasticity induced by natural and drug rewards and that, depending on the reward, repeated exposure to natural rewards might induce neuroplasticity that either promotes or counteracts addictive behavior.

  9. Reward circuitry function in autism during face anticipation and outcomes.

    PubMed

    Dichter, Gabriel S; Richey, J Anthony; Rittenberg, Alison M; Sabatino, Antoinette; Bodfish, James W

    2012-02-01

    The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary outcomes, participants with ASDs showed hyperactivation in left midfrontal and anterior cingulate gyrus. Groups did not differ in nucleus accumbens responses to faces. The ASD group demonstrated hyperactivation in bilateral amygdala during face anticipation that predicted social symptom severity and in bilateral insular cortex during face outcomes. These results add to the growing body of evidence that autism is characterized by altered functioning of reward circuitry. Additionally, atypical amygdala activation during the processing of social rewards may contribute to the development or expression of autistic features.

  10. Motivating inhibition - reward prospect speeds up response cancellation.

    PubMed

    Boehler, Carsten N; Hopf, Jens-Max; Stoppel, Christian M; Krebs, Ruth M

    2012-12-01

    Reward prospect has been demonstrated to facilitate various cognitive and behavioral operations, particularly by enhancing the speed and vigor of processes linked to approaching reward. Studies in this domain typically employed task regimes in which participants' overt responses are facilitated by prospective rewards. In contrast, we demonstrate here that even the cancellation of a motor response can be accelerated by reward prospect, thus signifying reward-related benefits on restraint rather than approach behavior. Importantly, this facilitation occurred independent of strategy-related adjustments of response speed, which are known to systematically distort the estimation of response-cancellation speed. The fact that motivational factors can indeed facilitate response inhibition is not only relevant for understanding how motivation and response inhibition interact in healthy participants but also for work on various patient groups that display response-inhibition deficits, suggesting that core differences in the ability to inhibit motor responses have to be differentiated from motivational factors.

  11. Exit, punishment and rewards in commons dilemmas: an experimental study.

    PubMed

    Bravo, Giangiacomo; Squazzoni, Flaminio

    2013-01-01

    Commons dilemmas are interaction situations where a common good is provided or exploited by a group of individuals so that optimal collective outcomes clash with private interests. Although in these situations, social norms and institutions exist that might help individuals to cooperate, little is known about the interaction effects between positive and negative incentives and exit options by individuals. We performed a modified public good game experiment to examine the effect of exit, rewards and punishment, as well as the interplay between exit and rewards and punishment. We found that punishment had a stronger effect than rewards on cooperation if considered by itself, whereas rewards had a stronger effect when combined with voluntary participation. This can be explained in terms of the 'framing effect', i.e., as the combination of exit and rewards might induce people to attach higher expected payoffs to cooperative strategies and expect better behaviour from others.

  12. No Apparent Influence of Reward upon Visual Statistical Learning

    PubMed Central

    Rogers, Leeland L.; Friedman, Kyle G.; Vickery, Timothy J.

    2016-01-01

    Humans are capable of detecting and exploiting a variety of environmental regularities, including stimulus-stimulus contingencies (e.g., visual statistical learning) and stimulus-reward contingencies. However, the relationship between these two types of learning is poorly understood. In two experiments, we sought evidence that the occurrence of rewarding events enhances or impairs visual statistical learning. Across all of our attempts to find such evidence, we employed a training stage during which we grouped shapes into triplets and presented triplets one shape at a time in an undifferentiated stream. Participants subsequently performed a surprise recognition task in which they were tested on their knowledge of the underlying structure of the triplets. Unbeknownst to participants, triplets were also assigned no-, low-, or high-reward status. In Experiments 1A and 1B, participants viewed shape streams while low and high rewards were “randomly” given, presented as low- and high-pitched tones played through headphones. Rewards were always given on the third shape of a triplet (Experiment 1A) or the first shape of a triplet (Experiment 1B), and high- and low-reward sounds were always consistently paired with the same triplets. Experiment 2 was similar to Experiment 1, except that participants were required to learn value associations of a subset of shapes before viewing the shape stream. Across all experiments, we observed significant visual statistical learning effects, but the strength of learning did not differ amongst no-, low-, or high-reward conditions for any of the experiments. Thus, our experiments failed to find any influence of rewards on statistical learning, implying that visual statistical learning may be unaffected by the occurrence of reward. The system that detects basic stimulus-stimulus regularities may operate independently of the system that detects reward contingencies. PMID:27853441

  13. No Apparent Influence of Reward upon Visual Statistical Learning.

    PubMed

    Rogers, Leeland L; Friedman, Kyle G; Vickery, Timothy J

    2016-01-01

    Humans are capable of detecting and exploiting a variety of environmental regularities, including stimulus-stimulus contingencies (e.g., visual statistical learning) and stimulus-reward contingencies. However, the relationship between these two types of learning is poorly understood. In two experiments, we sought evidence that the occurrence of rewarding events enhances or impairs visual statistical learning. Across all of our attempts to find such evidence, we employed a training stage during which we grouped shapes into triplets and presented triplets one shape at a time in an undifferentiated stream. Participants subsequently performed a surprise recognition task in which they were tested on their knowledge of the underlying structure of the triplets. Unbeknownst to participants, triplets were also assigned no-, low-, or high-reward status. In Experiments 1A and 1B, participants viewed shape streams while low and high rewards were "randomly" given, presented as low- and high-pitched tones played through headphones. Rewards were always given on the third shape of a triplet (Experiment 1A) or the first shape of a triplet (Experiment 1B), and high- and low-reward sounds were always consistently paired with the same triplets. Experiment 2 was similar to Experiment 1, except that participants were required to learn value associations of a subset of shapes before viewing the shape stream. Across all experiments, we observed significant visual statistical learning effects, but the strength of learning did not differ amongst no-, low-, or high-reward conditions for any of the experiments. Thus, our experiments failed to find any influence of rewards on statistical learning, implying that visual statistical learning may be unaffected by the occurrence of reward. The system that detects basic stimulus-stimulus regularities may operate independently of the system that detects reward contingencies.

  14. Motivational orientation modulates the neural response to reward.

    PubMed

    Linke, Julia; Kirsch, Peter; King, Andrea V; Gass, Achim; Hennerici, Michael G; Bongers, André; Wessa, Michèle

    2010-02-01

    Motivational orientation defines the source of motivation for an individual to perform a particular action and can either originate from internal desires (e.g., interest) or external compensation (e.g., money). To this end, motivational orientation should influence the way positive or negative feedback is processed during learning situations and this might in turn have an impact on the learning process. In the present study, we thus investigated whether motivational orientation, i.e., extrinsic and intrinsic motivation modulates the neural response to reward and punishment as well as learning from reward and punishment in 33 healthy individuals. To assess neural responses to reward, punishment and learning of reward contingencies we employed a probabilistic reversal learning task during functional magnetic resonance imaging. Extrinsic and intrinsic motivation were assessed with a self-report questionnaire. Rewarding trials fostered activation in the medial orbitofrontal cortex and anterior cingulate gyrus (ACC) as well as the amygdala and nucleus accumbens, whereas for punishment an increased neural response was observed in the medial and inferior prefrontal cortex, the superior parietal cortex and the insula. High extrinsic motivation was positively correlated to increased neural responses to reward in the ACC, amygdala and putamen, whereas a negative relationship between intrinsic motivation and brain activation in these brain regions was observed. These findings show that motivational orientation indeed modulates the responsiveness to reward delivery in major components of the human reward system and therefore extends previous results showing a significant influence of individual differences in reward-related personality traits on the neural processing of reward.

  15. Effort-reward imbalance and depression in Japanese medical residents.

    PubMed

    Sakata, Yumi; Wada, Koji; Tsutsumi, Akizumi; Ishikawa, Hiroyasu; Aratake, Yutaka; Watanabe, Mayumi; Katoh, Noritada; Aizawa, Yoshiharu; Tanaka, Katsutoshi

    2008-01-01

    The effort-reward imbalance is an important psychosocial factor which is related to poor health among employees. However, there are few studies that have evaluated effort-reward imbalance among medical residents. The present study was done to determine the association between psychosocial factors at work as defined by the effort-reward imbalance model and depression among Japanese medical residents. We distributed a questionnaire to 227 medical residents at 16 teaching hospitals in Japan at the end of August 2005. We asked participants to answer questions which included demographic information, depressive symptoms, effort-reward imbalance, over-commitment and social support. Depression was evaluated using the Japanese version of the Center for Epidemiologic Studies-Depression (CES-D) scale. The effort-reward imbalance and over-commitment were assessed by the Effort-Reward Imbalance (ERI) questionnaire which Siegrist developed. Social support was determined on a visual analog scale. Logistic regression analysis was performed to determine the associations between effort-reward imbalance and depressive symptoms. Depressive symptoms were found in 35 (29.2%) 1st-year residents and 21 (27.6%) 2nd-year residents. The effort-reward ratio >1 (OR, 8.83; 95% CI, 2.87-27.12) and low social support score (OR, 2.77, 95% CI, 1.36-5.64) were associated with depressive symptoms among medical residents. Effort-reward imbalance was independently related to depression among Japanese medical residents. The present study suggests that balancing between effort and reward at work is important for medical residents' mental health.

  16. Lateral Hypothalamic Circuits for Feeding and Reward

    PubMed Central

    Stuber, Garret D.; Wise, Roy A.

    2016-01-01

    In experiments conducted over 60 years ago, the lateral hypothalamic area (LHA) was identified as a critical neuroanatomical substrate for motivated behavior. Electrical stimulation of the LHA induces voracious feeding even in non-restricted animals. In the absence of food, animals will work tirelessly, often lever-pressing 1000’s of times per hour, for electrical stimulation at the same site that provokes feeding, drinking, and other species-typical motivated behaviors. Here we review the classic findings from electrical stimulation studies and integrate them with more recent work that has utilized contemporary circuit-based approaches to study the LHA. We identify specific anatomically and molecularly defined LHA elements that integrate diverse information arising from cortical, extended amygdala, and basal forebrain networks to ultimately generate a highly specified and invigorated behavioral state conveyed via LHA projections to downstream reward and feeding specific circuits. PMID:26814589

  17. Lateral hypothalamic circuits for feeding and reward.

    PubMed

    Stuber, Garret D; Wise, Roy A

    2016-02-01

    In experiments conducted over 60 years ago, the lateral hypothalamic area (LHA) was identified as a critical neuroanatomical substrate for motivated behavior. Electrical stimulation of the LHA induces voracious feeding even in well-fed animals. In the absence of food, animals will work tirelessly, often lever-pressing thousands of times per hour, for electrical stimulation at the same site that provokes feeding, drinking and other species-typical motivated behaviors. Here we review the classic findings from electrical stimulation studies and integrate them with more recent work that has used contemporary circuit-based approaches to study the LHA. We identify specific anatomically and molecularly defined LHA elements that integrate diverse information arising from cortical, extended amygdala and basal forebrain networks to ultimately generate a highly specified and invigorated behavioral state conveyed via LHA projections to downstream reward and feeding-specific circuits.

  18. Work Motivation and the Negative Effects of Extrinsic Rewards: A Reward With Implications for Theory and Practice

    ERIC Educational Resources Information Center

    Notz, William W.

    1975-01-01

    Summarizes and discusses findings on two hypotheses predicting interaction between intrinsic and extrinsic motivation: extrinsic rewards are those which provide satisfaction independent of the actual activity itself and are controlled by someone other than the employee, whereas intrinsic rewards are those over which the employee has a high degree…

  19. Walks with optimal reward on metric spaces

    NASA Astrophysics Data System (ADS)

    Behrends, Ehrhard

    2006-03-01

    Let (M, d) be a complete metric space and suppose that there are given finitely many contractions Γρ:M→ M and Lipschitz maps \\varphi_{\\rho}:M\\rightarrow{\\Bbb R} (ρ = 1, ..., r). We consider 'walks' of length m with a given starting point x0 in M. They are defined as follows: one chooses a sequence (ρμ)μ=1,..., m of length m in {1, ..., r}, and this choice induces the 'walk' \\[ \\begin{eqnarray*}\\fl x_{0},\\ x_{1}:=\\Gamma_{\\rho_{1}}(x_{0}),\\tqs x_{2}:=\\Gamma_{\\rho_{2}}(x_{1}), \\ldots,\\tqs x_{m}:=\\Gamma_{\\rho_{m}}(x_{m-1}).\\end{eqnarray*} \\] Associated with x1, ..., xm is the 'reward' \\[ \\begin{equation*}\\varphi_{\\rho_{1}}(x_{0})+\\varphi_{\\rho_{2}}(x_{1})+\\cdots+\\varphi_{\\rho_{m}}(x_{m-1}).\\end{equation*} \\] We denote by R^{\\max}_{x_{0}}(m) the maximal possible reward. The aim of this paper is to investigate the behaviour of the sequence (R^{\\max}_{x_{0}}(m)) for large m. It will be shown that the growth is nearly linear: there is a constant γ (which does not depend on x0) such that R^{\\max}_{x_{0}}(m)/m tends to γ. However, an explicit calculation of γ might be hard. The complexity depends on the fractal dimension of the smallest nonempty compact subset of M which is invariant with respect to all Γρ. In the case of finite M one can say much more. Then—after a suitable rescaling—the sequence (R^{\\max}_{x_{0}}(m)) is periodic where the length of the period can be described in terms of the length of certain cycles of a graph associated with M. The motivation to study this problem came from a variant of Parrondo's paradox from probability theory: what is the optimal choice of games if a great number of players is involved?

  20. The role of serotonin in reward, punishment and behavioural inhibition in humans: insights from studies with acute tryptophan depletion.

    PubMed

    Faulkner, Paul; Deakin, J F William

    2014-10-01

    Deakin and Graeff proposed that forebrain 5-hydroxytryptamine (5-HT) projections are activated by aversive events and mediate anticipatory coping responses including avoidance learning and suppression of the fight-flight escape/panic response. Other theories proposed 5-HT mediates aspects of behavioural inhibition or reward. Most of the evidence comes from rodent studies. We review 36 experimental studies in humans in which the technique of acute tryptophan depletion (ATD) was used to explicitly address the role of 5-HT in response inhibition, punishment and reward. ATD did not cause disinhibition of responding in the absence of rewards or punishments (9 studies). A major role for 5-HT in reward processing is unlikely but further tests are warranted by some ATD findings. Remarkably, ATD lessened the ability of punishments (losing points or notional money) to restrain behaviour without affecting reward processing in 7 studies. Two of these studies strongly indicate that ATD blocks 5-HT mediated aversively conditioned Pavlovian inhibition and this can explain a number of the behavioural effects of ATD.

  1. Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease.

    PubMed

    Nobili, Annalisa; Latagliata, Emanuele Claudio; Viscomi, Maria Teresa; Cavallucci, Virve; Cutuli, Debora; Giacovazzo, Giacomo; Krashia, Paraskevi; Rizzo, Francesca Romana; Marino, Ramona; Federici, Mauro; De Bartolo, Paola; Aversa, Daniela; Dell'Acqua, Maria Concetta; Cordella, Alberto; Sancandi, Marco; Keller, Flavio; Petrosini, Laura; Puglisi-Allegra, Stefano; Mercuri, Nicola Biagio; Coccurello, Roberto; Berretta, Nicola; D'Amelio, Marcello

    2017-04-03

    Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer's disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing.

  2. Toxoplasma gondii infection and testosterone congruently increase tolerance of male rats for risk of reward forfeiture.

    PubMed

    Tan, Donna; Vyas, Ajai

    2016-03-01

    Decision making under risk involves balancing the potential of gaining rewards with the possibility of loss and/or punishment. Tolerance to risk varies between individuals. Understanding the biological basis of risk tolerance is pertinent because excessive tolerance contributes to adverse health and safety outcomes. Yet, not much is known about biological factors mediating inter-individual variability in this regard. We investigate if latent Toxoplasma gondii infection can cause risk tolerance. Using a rodent model of the balloon analogous risk task, we show that latent T. gondii infection leads to a greater tolerance of reward forfeiture. Furthermore, effects of the infection on risk can be recapitulated with testosterone supplementation alone, demonstrating that greater testosterone synthesis by the host post-infection is sufficient to change risk tolerance. T. gondii is a frequent parasite of humans and animals. Thus, the infection status can potentially explain some of the inter-individual variability in the risky decision making.

  3. Brain Rewarding Stimulation Reduces Extracellular Glutamate Through Glial Modulation in Medial Prefrontal Cortex of Rats.

    PubMed

    Murakami, Gen; Nakamura, Masato; Takita, Masatoshi; Ishida, Yasushi; Ueki, Takatoshi; Nakahara, Daiichiro

    2015-11-01

    Growing evidence implicates a critical involvement of prefrontal glial modulation of extracellular glutamate (GLU) in aversive behaviors. However, nothing is known about whether prefrontal glial cells modulate GLU levels in rewarding behaviors. To address this question, we measured GLU efflux in the medial prefrontal cortex (PFC) of rats associated with rewarding behaviors. We used intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB) as the rewarding behavior. GLU was indirectly measured using microdialysis combined with on-line fluorometric detection of NADH resulting from the reaction of GLU and NAD(+) catalyzed by GLU dehydrogenase with a time resolution of 1 min. ICSS caused a minute-by-minute change of extracellular GLU in the medial PFC, with a slight decrease during the stimulation, followed by an increase afterward. This bidirectional change was tetrodotoxin insensitive and abolished by the gliotoxin fluorocitrate. To confirm and extend the previous studies of aversion-induced increase of extracellular GLU in the medial PFC, we also measured prefrontal GLU efflux associated with an aversive stimulation, immobilization stress. The temporal change in extracellular GLU caused by this stress was markedly different from that observed during ICSS. A rapid increase in GLU was detected during the aversive stimulation, followed by a large increase afterward. This bimodal change was tetrodotoxin insensitive, similar to that detected for ICSS. These findings indicate a bidirectional regulation of extracellular GLU by prefrontal glial cells associated with rat ICSS behavior, and reveal that glial modulation of GLU neurochemistry in the medial PFC contributes to rewarding as well as aversive behaviors in rats.

  4. Aversive Counterconditioning Attenuates Reward Signaling in the Ventral Striatum

    PubMed Central

    Kaag, Anne Marije; Schluter, Renée S.; Karel, Peter; Homberg, Judith; van den Brink, Wim; Reneman, Liesbeth; van Wingen, Guido A.

    2016-01-01

    Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient reward such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional magnetic resonance imaging (fMRI). In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signaling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signaling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula. PMID:27594829

  5. Anticipatory pleasure predicts motivation for reward in major depression.

    PubMed

    Sherdell, Lindsey; Waugh, Christian E; Gotlib, Ian H

    2012-02-01

    Anhedonia, the lack of interest or pleasure in response to hedonic stimuli or experiences, is a cardinal symptom of depression. This deficit in hedonic processing has been posited to influence depressed individuals' motivation to engage in potentially rewarding experiences. Accumulating evidence indicates that hedonic processing is not a unitary construct but rather consists of an anticipatory and a consummatory phase. We examined how these components of hedonic processing influence motivation to obtain reward in participants diagnosed with major depression and in never-disordered controls. Thirty-eight currently depressed and 30 never-disordered control participants rated their liking of humorous and nonhumorous cartoons and then made a series of choices between viewing a cartoon from either group. Each choice was associated with a specified amount of effort participants would have to exert before viewing the chosen cartoon. Although depressed and control participants did not differ in their consummatory liking of the rewards, levels of reward liking predicted motivation to expend effort for the rewards only in the control participants; in the depressed participants, liking and motivation were dissociated. In the depressed group, levels of anticipatory anhedonia predicted motivation to exert effort for the rewards. These findings support the formulation that anhedonia is not a unitary construct and suggest that, for depressed individuals, deficits in motivation for reward are driven primarily by low anticipatory pleasure and not by decreased consummatory liking.

  6. Working memory and reward association learning impairments in obesity

    PubMed Central

    Coppin, Géraldine; Nolan-Poupart, Sarah; Jones-Gotman, Marilyn; Small, Dana M.

    2014-01-01

    Obesity has been associated with impaired executive functions including working memory. Less explored is the influence of obesity on learning and memory. In the current study we assessed stimulus reward association learning, explicit learning and memory and working memory in healthy weight, overweight and obese individuals. Explicit learning and memory did not differ as a function of group. In contrast, working memory was significantly and similarly impaired in both overweight and obese individuals compared to the healthy weight group. In the first reward association learning task the obese, but not healthy weight or overweight participants consistently formed paradoxical preferences for a pattern associated with a negative outcome (fewer food rewards). To determine if the deficit was specific to food reward a second experiment was conducted using money. Consistent with experiment 1, obese individuals selected the pattern associated with a negative outcome (fewer monetary rewards) more frequently than healthy weight individuals and thus failed to develop a significant preference for the most rewarded patterns as was observed in the healthy weight group. Finally, on a probabilistic learning task, obese compared to healthy weight individuals showed deficits in negative, but not positive outcome learning. Taken together, our results demonstrate deficits in working memory and stimulus reward learning in obesity and suggest that obese individuals are impaired in learning to avoid negative outcomes. PMID:25447070

  7. Anticipatory Pleasure Predicts Motivation for Reward in Major Depression

    PubMed Central

    Sherdell, Lindsey; Waugh, Christian E.; Gotlib, Ian H.

    2012-01-01

    Anhedonia, the lack of interest or pleasure in response to hedonic stimuli or experiences, is a cardinal symptom of depression. This deficit in hedonic processing has been posited to influence depressed individuals’ motivation to engage in potentially rewarding experiences. Accumulating evidence indicates that hedonic processing is not a unitary construct but rather consists of an anticipatory and a consummatory phase. We examined how these components of hedonic processing influence motivation to obtain reward in participants diagnosed with major depression and in never-disordered controls. Thirty-eight currently depressed and 30 never-disordered control participants rated their liking of humorous and nonhumorous cartoons and then made a series of choices between viewing a cartoon from either group. Each choice was associated with a specified amount of effort participants would have to exert before viewing the chosen cartoon. Although depressed and control participants did not differ in their consummatory liking of the rewards, levels of reward liking predicted motivation to expend effort for the rewards only in the control participants; in the depressed participants, liking and motivation were dissociated. In the depressed group, levels of anticipatory anhedonia predicted motivation to exert effort for the rewards. These findings support the formulation that anhedonia is not a unitary construct and suggest that, for depressed individuals, deficits in motivation for reward are driven primarily by low anticipatory pleasure and not by decreased consummatory liking. PMID:21842963

  8. Influence of reward motivation on human declarative memory.

    PubMed

    Miendlarzewska, Ewa A; Bavelier, Daphne; Schwartz, Sophie

    2016-02-01

    Motivational relevance can prioritize information for memory encoding and consolidation based on reward value. In this review, we pinpoint the possible psychological and neural mechanisms by which reward promotes learning, from guiding attention to enhancing memory consolidation. We then discuss how reward value can spill-over from one conditioned stimulus to a non-conditioned stimulus. Such generalization can occur across perceptually similar items or through more complex relations, such as associative or logical inferences. Existing evidence suggests that the neurotransmitter dopamine boosts the formation of declarative memory for rewarded information and may also control the generalization of reward values. In particular, temporally-correlated activity in the hippocampus and in regions of the dopaminergic circuit may mediate value-based decisions and facilitate cross-item integration. Given the importance of generalization in learning, our review points to the need to study not only how reward affects later memory but how learned reward values may generalize to related representations and ultimately alter memory structure.

  9. Auditory attentional selection is biased by reward cues

    PubMed Central

    Asutay, Erkin; Västfjäll, Daniel

    2016-01-01

    Auditory attention theories suggest that humans are able to decompose the complex acoustic input into separate auditory streams, which then compete for attentional resources. How this attentional competition is influenced by motivational salience of sounds is, however, not well-understood. Here, we investigated whether a positive motivational value associated with sounds could bias the attentional selection in an auditory detection task. Participants went through a reward-learning period, where correct attentional selection of one stimulus (CS+) lead to higher rewards compared to another stimulus (CS−). We assessed the impact of reward-learning by comparing perceptual sensitivity before and after the learning period, when CS+ and CS− were presented as distractors for a different target. Performance decreased after reward-learning when CS+ was a distractor, while it increased when CS− was a distractor. Thus, the findings show that sounds that were associated with high rewards captures attention involuntarily. Additionally, when successful inhibition of a particular sound (CS−) was associated with high rewards then it became easier to ignore it. The current findings have important implications for the understanding of the organizing principles of auditory perception and provide, for the first time, clear behavioral evidence for reward-dependent attentional learning in the auditory domain in humans. PMID:27841363

  10. Reward and punishment act as distinct factors in guiding behavior.

    PubMed

    Kubanek, Jan; Snyder, Lawrence H; Abrams, Richard A

    2015-06-01

    Behavior rests on the experience of reinforcement and punishment. It has been unclear whether reinforcement and punishment act as oppositely valenced components of a single behavioral factor, or whether these two kinds of outcomes play fundamentally distinct behavioral roles. To this end, we varied the magnitude of a reward or a penalty experienced following a choice using monetary tokens. The outcome of each trial was independent of the outcome of the previous trial, which enabled us to isolate and study the effect on behavior of each outcome magnitude in single trials. We found that a reward led to a repetition of the previous choice, whereas a penalty led to an avoidance of the previous choice. Surprisingly, the effects of the reward magnitude and the penalty magnitude revealed a pronounced asymmetry. The choice repetition effect of a reward scaled with the magnitude of the reward. In a marked contrast, the avoidance effect of a penalty was flat, not influenced by the magnitude of the penalty. These effects were mechanistically described using a reinforcement learning model after the model was updated to account for the penalty-based asymmetry. The asymmetry in the effects of the reward magnitude and the punishment magnitude was so striking that it is difficult to conceive that one factor is just a weighted or transformed form of the other factor. Instead, the data suggest that rewards and penalties are fundamentally distinct factors in governing behavior.

  11. The absence of reward induces inequity aversion in dogs

    PubMed Central

    Range, Friederike; Horn, Lisa; Viranyi, Zsófia; Huber, Ludwig

    2009-01-01

    One crucial element for the evolution of cooperation may be the sensitivity to others' efforts and payoffs compared with one's own costs and gains. Inequity aversion is thought to be the driving force behind unselfish motivated punishment in humans constituting a powerful device for the enforcement of cooperation. Recent research indicates that non-human primates refuse to participate in cooperative problem-solving tasks if they witness a conspecific obtaining a more attractive reward for the same effort. However, little is known about non-primate species, although inequity aversion may also be expected in other cooperative species. Here, we investigated whether domestic dogs show sensitivity toward the inequity of rewards received for giving the paw to an experimenter on command in pairs of dogs. We found differences in dogs tested without food reward in the presence of a rewarded partner compared with both a baseline condition (both partners rewarded) and an asocial control situation (no reward, no partner), indicating that the presence of a rewarded partner matters. Furthermore, we showed that it was not the presence of the second dog but the fact that the partner received the food that was responsible for the change in the subjects' behavior. In contrast to primate studies, dogs did not react to differences in the quality of food or effort. Our results suggest that species other than primates show at least a primitive version of inequity aversion, which may be a precursor of a more sophisticated sensitivity to efforts and payoffs of joint interactions. PMID:19064923

  12. Neuronal Reward and Decision Signals: From Theories to Data.

    PubMed

    Schultz, Wolfram

    2015-07-01

    Rewards are crucial objects that induce learning, approach behavior, choices, and emotions. Whereas emotions are difficult to investigate in animals, the learning function is mediated by neuronal reward prediction error signals which implement basic constructs of reinforcement learning theory. These signals are found in dopamine neurons, which emit a global reward signal to striatum and frontal cortex, and in specific neurons in striatum, amygdala, and frontal cortex projecting to select neuronal populations. The approach and choice functions involve subjective value, which is objectively assessed by behavioral choices eliciting internal, subjective reward preferences. Utility is the formal mathematical characterization of subjective value and a prime decision variable in economic choice theory. It is coded as utility prediction error by phasic dopamine responses. Utility can incorporate various influences, including risk, delay, effort, and social interaction. Appropriate for formal decision mechanisms, rewards are coded as object value, action value, difference value, and chosen value by specific neurons. Although all reward, reinforcement, and decision variables are theoretical constructs, their neuronal signals constitute measurable physical implementations and as such confirm the validity of these concepts. The neuronal reward signals provide guidance for behavior while constraining the free will to act.

  13. Neuronal Reward and Decision Signals: From Theories to Data

    PubMed Central

    Schultz, Wolfram

    2015-01-01

    Rewards are crucial objects that induce learning, approach behavior, choices, and emotions. Whereas emotions are difficult to investigate in animals, the learning function is mediated by neuronal reward prediction error signals which implement basic constructs of reinforcement learning theory. These signals are found in dopamine neurons, which emit a global reward signal to striatum and frontal cortex, and in specific neurons in striatum, amygdala, and frontal cortex projecting to select neuronal populations. The approach and choice functions involve subjective value, which is objectively assessed by behavioral choices eliciting internal, subjective reward preferences. Utility is the formal mathematical characterization of subjective value and a prime decision variable in economic choice theory. It is coded as utility prediction error by phasic dopamine responses. Utility can incorporate various influences, including risk, delay, effort, and social interaction. Appropriate for formal decision mechanisms, rewards are coded as object value, action value, difference value, and chosen value by specific neurons. Although all reward, reinforcement, and decision variables are theoretical constructs, their neuronal signals constitute measurable physical implementations and as such confirm the validity of these concepts. The neuronal reward signals provide guidance for behavior while constraining the free will to act. PMID:26109341

  14. Transient activation of midbrain dopamine neurons by reward risk.

    PubMed

    Fiorillo, C D

    2011-12-01

    Dopamine neurons of the ventral midbrain are activated transiently following stimuli that predict future reward. This response has been shown to signal the expected value of future reward, and there is strong evidence that it drives positive reinforcement of stimuli and actions associated with reward in accord with reinforcement learning models. Behavior is also influenced by reward uncertainty, or risk, but it is not known whether the transient response of dopamine neurons is sensitive to reward risk. To investigate this, monkeys were trained to associate distinct visual stimuli with certain or uncertain volumes of juice of nearly the same expected value. In a choice task, monkeys preferred the stimulus predicting an uncertain (risky) reward outcome. In a Pavlovian task, in which the neuronal responses to each stimulus could be measured in isolation, it was found that dopamine neurons were more strongly activated by the stimulus associated with reward risk. Given extensive evidence that dopamine drives reinforcement, these results strongly suggest that dopamine neurons can reinforce risk-seeking behavior (gambling), at least under certain conditions. Risk-seeking behavior has the virtue of promoting exploration and learning, and these results support the hypothesis that dopamine neurons represent the value of exploration.

  15. Influence of reward on corticospinal excitability during movement preparation.

    PubMed

    Klein, Pierre-Alexandre; Olivier, Etienne; Duque, Julie

    2012-12-12

    Current models of decision making postulate that action selection entails a competition within motor-related areas. According to this view, during action selection, motor activity should integrate cognitive information (e.g., reward) that drives our decisions. We tested this hypothesis in humans by measuring motor-evoked potentials (MEPs) in a left finger muscle during motor preparation in a hand selection task, in which subjects performed left or right key presses according to an imperative signal. This signal was either obvious or ambiguous, but subjects were always asked to react as fast as possible. When the signal was really indistinct, any key press was regarded as correct, so subjects could respond "at random" in those trials. A score based on reaction times was provided after each correct response, and subjects were told they would receive a monetary reward proportional to their final score. Importantly, the scores were either equitable for both hands or favored implicitly left responses (reward(neutral) and reward(biased) blocks, respectively). We found that subjects selected their left hand more often in the reward(biased) than in the reward(neutral) condition, particularly after ambiguous signals. Moreover, left MEPs were larger, as soon as the signal appeared, in the reward(biased) than in the reward(neutral) conditions. During the course of motor preparation, this effect became strongest following ambiguous signals, a condition in which subjects' choices relied strongly on the reward. These results indicate that motor activity is shaped by a cognitive variable that drives our choices, possibly in the context of a competition taking place within motor-related areas.

  16. Reward anticipation enhances brain activation during response inhibition.

    PubMed

    Rosell-Negre, Patricia; Bustamante, Juan Carlos; Fuentes-Claramonte, Paola; Costumero, Víctor; Benabarre, Sergio; Barros-Loscertales, Alfonso

    2014-06-01

    The chance to achieve a reward starts up the required neurobehavioral mechanisms to adapt our thoughts and actions in order to accomplish our objective. However, reward does not equally reinforce everybody but depends on interindividual motivational dispositions. Thus, immediate reward contingencies can modulate the cognitive process required for goal achievement, while individual differences in personality can affect this modulation. We aimed to test the interaction between inhibition-related brain response and motivational processing in a stop signal task by reward anticipation and whether individual differences in sensitivity to reward (SR) modulate such interaction. We analyzed the cognitive-motivational interaction between the brain pattern activation of the regions involved in correct and incorrect response inhibition and the association between such brain activations and SR scores. We also analyzed the behavioral effects of reward on both reaction times for the "go" trials before and after correct and incorrect inhibition in order to test error prediction performance and postinhibition adjustment. Our results show enhanced activation during response inhibition under reward contingencies in frontal, parietal, and subcortical areas. Moreover, activation of the right insula and the left putamen positively correlates with the SR scores. Finally, the possibility of reward outcome affects not only response inhibition performance (e.g., reducing stop signal reaction time), but also error prediction performance and postinhibition adjustment. Therefore, reward contingencies improve behavioral performance and enhance brain activation during response inhibition, and SR is related to brain activation. Our results suggest the conditions and factors that subserve cognitive control strategies in cognitive motivational interactions during response inhibition.

  17. Food reward. What it is and how to measure it.

    PubMed

    Rogers, Peter J; Hardman, Charlotte A

    2015-07-01

    We investigated the contribution of hunger and food liking to food reward, and the relationship between food reward and food intake. We defined liking as the pleasantness of taste of food in the mouth, and food reward as the momentary value of a food to the individual at the time of ingestion. Liking and food reward were measured, respectively, by ratings of the pleasantness of the taste of a mouthful, and ratings of desire to eat a portion, of the food in question. Hunger, which we view as primarily the absence of fullness, was rated without food being present. Study 1 provided evidence that hunger and liking contribute independently to food reward, with little effect of hunger on liking. Food intake reduced liking and reward value more for the eaten food than uneaten foods. The results were ambiguous as to whether this food-specific decline in reward value ('sensory-specific satiety') involved a decrease in 'wanting' in addition to the decrease in liking. Studies 2 and 3 compared desire to eat ratings with work-for-food and pay-for-food measures of food reward, and found desire to eat to be equal or superior in respect of effects of hunger and liking, and superior in predicting ad libitum food intake. A further general observation was that in making ratings of food liking participants may confuse the pleasantness of the taste of food with the pleasantness of eating it. The latter, which some call 'palatability,' decreases more with eating because it is significantly affected by hunger/fullness. Together, our results demonstrate the validity of ratings of desire to eat a portion of a tasted food as a measure of food reward and as a predictor of food intake.

  18. Modulation of corticospinal excitability by reward depends on task framing

    PubMed Central

    Mooshagian, Eric; Keisler, Aysha; Zimmermann, Trelawny; Schweickert, Janell M.; Wassermann, Eric M.

    2015-01-01

    Findings from previous transcranial magnetic stimulation (TMS) experiments suggest that the primary motor cortex (M1) is sensitive to reward conditions in the environment. However, the nature of this influence on M1 activity is poorly understood. The dopamine neuron response to conditioned stimuli encodes reward probability and outcome uncertainty, or the extent to which the outcome of a situation is known. Reward uncertainty and probability are related: uncertainty is maximal when probability is 0.5 and minimal when probability is 0 or 1 (i.e., certain outcome). Previous TMS-reward studies did not examine these factors independently. Here, we used single-pulse TMS to measure corticospinal excitability in 40 individuals while they performed a simple computer task, making guesses to find or avoid a hidden target. The task stimuli implied three levels of reward probability and two levels of uncertainty. We found that reward probability level interacted with the trial search condition. That is, motor evoked potential (MEP) amplitude, a measure of corticospinal neuron excitability, increased with increasing reward probability when participants were instructed to “find” a target, but not when they were instructed to “avoid” a target. There was no effect of uncertainty on MEPs. Response times varied with the number of choices. A subset of participants also received paired-pulse stimulation to evaluate changes in short-intracortical inhibition (SICI). No effects of SICI were observed. Taken together, the results suggest that the reward-contingent modulation of M1 activity reflects reward probability or a related aspect of utility, not outcome uncertainty, and that this effect is sensitive to the conceptual framing of the task. PMID:25543022

  19. The role of rewards in motivating participation in simple warfare.

    PubMed

    Glowacki, Luke; Wrangham, Richard W

    2013-12-01

    In the absence of explicit punitive sanctions, why do individuals voluntarily participate in intergroup warfare when doing so incurs a mortality risk? Here we consider the motivation of individuals for participating in warfare. We hypothesize that in addition to other considerations, individuals are incentivized by the possibility of rewards. We test a prediction of this "cultural rewards war-risk hypothesis" with ethnographic literature on warfare in small-scale societies. We find that a greater number of benefits from warfare is associated with a higher rate of death from conflict. This provides preliminary support for the relationship between rewards and participation in warfare.

  20. Reconsidering Food Reward, Brain Stimulation, and Dopamine: Incentives Act Forward.

    PubMed

    Newquist, Gunnar; Gardner, R Allen

    2015-01-01

    In operant conditioning, rats pressing levers and pigeons pecking keys depend on contingent food reinforcement. Food reward agrees with Skinner's behaviorism, undergraduate textbooks, and folk psychology. However, nearly a century of experimental evidence shows, instead, that food in an operant conditioning chamber acts forward to evoke species-specific feeding behavior rather than backward to reinforce experimenter-defined responses. Furthermore, recent findings in neuroscience show consistently that intracranial stimulation to reward centers and dopamine release, the proposed reward molecule, also act forward to evoke inborn species-specific behavior. These results challenge longstanding views of hedonic learning and must be incorporated into contemporary learning theory.

  1. Human choices between variable and fixed rewards in hypothetical variable-delay and double-reward discounting procedures.

    PubMed

    McKerchar, Todd L; Mazur, James E

    2016-07-01

    Prior research has shown that nonhumans show an extreme preference for variable- over fixed-delays to reinforcement. This well-established preference for variability occurs because a reinforcer's strength or "value" decreases according to a curvilinear function as its delay increases. The purpose of the present experiments was to investigate whether this preference for variability occurs with human participants making hypothetical choices. In three experiments, participants recruited from Amazon Mechanical Turk made choices between variable and fixed monetary rewards. In a variable-delay procedure, participants repeatedly chose between a reward delivered either immediately or after a delay (with equal probability) and a reward after a fixed delay (Experiments 1 and 2). In a double-reward procedure, participants made choices between an alternative consisting of two rewards, one delivered immediately and one after a delay, and a second alternative consisting of a single reward delivered after a delay (Experiments 1 and 3). Finally, all participants completed a standard delay-discounting task. Although we observed both curvilinear discounting and magnitude effects in the standard discounting task, we found no consistent evidence of a preference for variability-as predicted by two prominent models of curvilinear discounting (i.e., a simple hyperbola and a hyperboloid)-in our variable-delay and double-reward procedures. This failure to observe a preference for variability may be attributed to the hypothetical, rule-governed nature of choices in the present study. In such contexts, participants may adopt relatively simple strategies for making more complex choices.

  2. Inverted Social Reward: Associations between Psychopathic Traits and Self-Report and Experimental Measures of Social Reward

    PubMed Central

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

    2014-01-01

    Individuals with high levels of psychopathic traits tend to undervalue long-term, affiliative relationships, but it remains unclear what motivates them to engage in social interactions at all. Their experience of social reward may provide an important clue. In Study 1 of this paper, a large sample of participants (N = 505) completed a measure of psychopathic traits (Self-Report Psychopathy Scale Short-Form) and a measure of social reward value (Social Reward Questionnaire) to explore what aspects of social reward are associated with psychopathic traits. In Study 2 (N = 110), the same measures were administered to a new group of participants along with two experimental tasks investigating monetary and social reward value. Psychopathic traits were found to be positively correlated with the enjoyment of callous treatment of others and negatively associated with the enjoyment of positive social interactions. This indicates a pattern of ‘inverted’ social reward in which being cruel is enjoyable and being kind is not. Interpersonal psychopathic traits were also positively associated with the difference between mean reaction times (RTs) in the monetary and social experimental reward tasks; individuals with high levels of these traits responded comparatively faster to social than monetary reward. We speculate that this may be because social approval/admiration has particular value for these individuals, who have a tendency to use and manipulate others. Together, these studies provide evidence that the self-serving and cruel social behaviour seen in psychopathy may in part be explained by what these individuals find rewarding. PMID:25162519

  3. Behavioral and neural evidence of incentive bias for immediate rewards relative to preference-matched delayed rewards

    PubMed Central

    Luo, Shan; Ainslie, George; Giragosian, Lisa; Monterosso, John R.

    2010-01-01

    Several theories of self-control (including intertemporal bargaining Ainslie (1992) and self-signaling Bodner and Prelec (2001)) imply that intertemporal decisions can be more farsighted than would be predicted by the incentive associated with rewards outside a decision context. We examined this hypothesis using behavior and functional neuroimaging. First, subjects expressed preferences between amounts of money delayed by four months and smaller amounts available that day. This allowed us to establish “indifference pairs” individualized to each participant -- immediate and delayed amounts that were equally preferred. Participants subsequently performed a reaction time fMRI task (Knutson et al, 2001a) that provided them with distinct opportunities to win each of the rewards that comprised the indifference pairs. Anatomical Region of Interest analysis as well as whole-brain analysis indicated greater response recruited by the immediate rewards (relative to the preference matched delayed rewards) in regions previously implicated as sensitive to incentive value using the same task (including bilateral putamen, bilateral anterior insula and midbrain). RT to the target was also faster during the immediate relative to delayed reward trials (p < .01), and individual differences in RT between immediate versus delayed reward trials correlated with variance in MR signal in those clusters that responded preferentially to immediate rewards (r = .33, p < .05). These findings indicate a discrepancy in incentive associated with the immediate versus the preference-matched delayed rewards. This discrepancy may mark the contribution of self-control processes that are recruited during decision-making, but that are absent when rewards are individually anticipated. PMID:19940177

  4. Pleiotrophin differentially regulates the rewarding and sedative effects of ethanol.

    PubMed

    Vicente-Rodríguez, Marta; Pérez-García, Carmen; Ferrer-Alcón, Marcel; Uribarri, María; Sánchez-Alonso, María G; Ramos, María P; Herradón, Gonzalo

    2014-12-01

    Pleiotrophin (PTN) is a cytokine with important roles in dopaminergic neurons. We found that an acute ethanol (2.0 g/kg, i.p.) administration causes a significant up-regulation of PTN mRNA and protein levels in the mouse prefrontal cortex, suggesting that endogenous PTN could modulate behavioural responses to ethanol. To test this hypothesis, we studied the behavioural effects of ethanol in PTN knockout (PTN(-/-) ) mice and in mice with cortex- and hippocampus-specific transgenic PTN over-expression (PTN-Tg). Ethanol (1.0 and 2.0 g/kg) induced an enhanced conditioned place preference in PTN(-/-) compared to wild type mice, suggesting that PTN prevents ethanol rewarding effects. Accordingly, the conditioning effects of ethanol were completely abolished in PTN-Tg mice. The ataxic effects induced by ethanol (2.0 g/kg) were not affected by the genotype. However, the sedative effects of ethanol (3.6 g/kg) tested in a loss of righting reflex paradigm were significantly reduced in PTN-Tg mice, suggesting that up-regulation of PTN levels prevents the sedative effects of ethanol. These results indicate that PTN may be a novel genetic factor of importance in alcohol use disorders, and that potentiation of the PTN signalling pathway may be a promising therapeutic strategy in the treatment of these disorders.

  5. Cannabis reward: biased towards the fairer sex?

    PubMed

    McGregor, I S; Arnold, J C

    2007-11-01

    In contrast to drugs such as alcohol, amphetamine and cocaine, cannabis use in humans has proven difficult to model in laboratory animals. Recent breakthrough discoveries of intravenous THC self-administration in rhesus monkeys and self-administration of the synthetic cannabinoid agonist WIN 55,212-2 in rats have allowed new studies of the genetic, neural and environmental determinants of cannabis use. In the present issue of BJP, Fattore and colleagues further demonstrate genetic (strain) differences in WIN 55,212-2 self-administration in rats, with Long Evans (LE) and Lister Hooded (LH), but not Sprague-Dawley, rats self-administering this drug. They then show that female LE and LH rats self-administer more WIN 55,212-2 than male rats. Ovariectomy abolished this sex difference, suggesting a permissive role for oestrogen in cannabis reward. This accompanying Commentary reviews recent progress in animal models of cannabis use and highlights the role of genetic, developmental and endocrine factors in driving cannabis use and dependence.

  6. Perspective: Recognizing and rewarding clinical scholarship.

    PubMed

    Grigsby, R Kevin; Thorndyke, Luanne

    2011-01-01

    Faculty members in medical schools and academic medical centers are in a constant process of generating new knowledge. The cornerstone of academia--and academic medicine--is scholarship. Traditionally, tenure and/or academic promotion in the professorial ranks is awarded to those who meet institutional criteria in the missions of research, teaching, and service, including patient care. In the academic review process, priority is often placed on a record of demonstrated, consistent success in traditional laboratory research, also known as the scholarship of discovery. More recently, there has been greater recognition of other forms of scholarship: education, application, and integration. These forms of scholarship, although less recognized, also result in the generation of new knowledge. In an attempt to understand the breadth and scope of clinical scholarship, the authors searched the extant literature in academic medicine for a definition of clinical scholarship and expanded the search to disciplines outside of medicine. They found that succinct, discrete definitions of clinical scholarship have been published in other disciplines, but not in academic medicine. After reviewing definitions of clinical scholarship from other disciplines, adapting definitions of educational scholarship in academic medicine, and including qualities unique to clinical scholarship, the authors developed a framework for understanding clinical scholarship in academic medicine as a means for opening a dialogue within the academic medical community. This dialogue hopefully will lead to formulating a succinct, discrete definition of clinical scholarship that will allow greater recognition and reward for clinical scholars in the promotion and tenure process.

  7. Psychological distance to reward: A human replication

    PubMed Central

    Leung, Jin-Pang

    1989-01-01

    Choice behavior in college students was examined in two experiments using the concurrent-chains procedure. In both experiments, the concurrent chains were presented on a microcomputer in the form of an air-defense game in which subjects used two radar systems to detect and subsequently destroy enemy aircraft. Access to one of two radar systems was controlled by a pair of independent concurrent variable-interval 60-s schedules with a 4-s changeover delay always in effect. In the terminal link, the appearance of an enemy aircraft was determined by a pair of differentially segmented fixed-time schedules (Experiment 1) or fixed-interval schedules (Experiment 2) of equal overall duration. In Experiment 1, the terminal-link duration was either 20 s or 40 s, and subjects preferred the unsegmented to the segmented intervals. In Experiment 2, the duration was either 10 s or 60 s, and the reinforcement contingencies required responding during the terminal link. Prior to the reinstatement of the initial link, subjects estimated the duration of the terminal-link schedule. Segmentation affected choice in the 60-s conditions but not in the 10-s ones. Preference for the unsegmented schedule was correlated with an overestimation of the durations for the segmented schedules. These results replicated those found in animal experiments and support the notion of increasing the psychological distance to reward by segmenting a time-based schedule of reinforcement. PMID:16812581

  8. Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.

    PubMed

    Rogers, R D; Owen, A M; Middleton, H C; Williams, E J; Pickard, J D; Sahakian, B J; Robbins, T W

    1999-10-15

    Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

  9. Optogenetic Mimicry of the Transient Activation of Dopamine Neurons by Natural Reward Is Sufficient for Operant Reinforcement

    PubMed Central

    Kim, Kyung Man; Baratta, Michael V.; Yang, Aimei; Lee, Doheon; Boyden, Edward S.; Fiorillo, Christopher D.

    2012-01-01

    Activation of dopamine receptors in forebrain regions, for minutes or longer, is known to be sufficient for positive reinforcement of stimuli and actions. However, the firing rate of dopamine neurons is increased for only about 200 milliseconds following natural reward events that are better than expected, a response which has been described as a “reward prediction error” (RPE). Although RPE drives reinforcement learning (RL) in computational models, it has not been possible to directly test whether the transient dopamine signal actually drives RL. Here we have performed optical stimulation of genetically targeted ventral tegmental area (VTA) dopamine neurons expressing Channelrhodopsin-2 (ChR2) in mice. We mimicked the transient activation of dopamine neurons that occurs in response to natural reward by applying a light pulse of 200 ms in VTA. When a single light pulse followed each self-initiated nose poke, it was sufficient in itself to cause operant reinforcement. Furthermore, when optical stimulation was delivered in separate sessions according to a predetermined pattern, it increased locomotion and contralateral rotations, behaviors that are known to result from activation of dopamine neurons. All three of the optically induced operant and locomotor behaviors were tightly correlated with the number of VTA dopamine neurons that expressed ChR2, providing additional evidence that the behavioral responses were caused by activation of dopamine neurons. These results provide strong evidence that the transient activation of dopamine neurons provides a functional reward signal that drives learning, in support of RL theories of dopamine function. PMID:22506004

  10. Optogenetic mimicry of the transient activation of dopamine neurons by natural reward is sufficient for operant reinforcement.

    PubMed

    Kim, Kyung Man; Baratta, Michael V; Yang, Aimei; Lee, Doheon; Boyden, Edward S; Fiorillo, Christopher D

    2012-01-01

    Activation of dopamine receptors in forebrain regions, for minutes or longer, is known to be sufficient for positive reinforcement of stimuli and actions. However, the firing rate of dopamine neurons is increased for only about 200 milliseconds following natural reward events that are better than expected, a response which has been described as a "reward prediction error" (RPE). Although RPE drives reinforcement learning (RL) in computational models, it has not been possible to directly test whether the transient dopamine signal actually drives RL. Here we have performed optical stimulation of genetically targeted ventral tegmental area (VTA) dopamine neurons expressing Channelrhodopsin-2 (ChR2) in mice. We mimicked the transient activation of dopamine neurons that occurs in response to natural reward by applying a light pulse of 200 ms in VTA. When a single light pulse followed each self-initiated nose poke, it was sufficient in itself to cause operant reinforcement. Furthermore, when optical stimulation was delivered in separate sessions according to a predetermined pattern, it increased locomotion and contralateral rotations, behaviors that are known to result from activation of dopamine neurons. All three of the optically induced operant and locomotor behaviors were tightly correlated with the number of VTA dopamine neurons that expressed ChR2, providing additional evidence that the behavioral responses were caused by activation of dopamine neurons. These results provide strong evidence that the transient activation of dopamine neurons provides a functional reward signal that drives learning, in support of RL theories of dopamine function.

  11. A cholinergic mechanism for reward timing within primary visual cortex

    PubMed Central

    Chubykin, Alexander A.; Roach, Emma B.; Bear, Mark F.; Shuler, Marshall G. Hussain

    2013-01-01

    Summary Neurons in rodent primary visual cortex (V1) relate operantly conditioned stimulus-reward intervals with modulated patterns of spiking output, but little is known about the locus or mechanism of this plasticity. Here we show that cholinergic basal forebrain projections to V1 are necessary for the neural acquisition, but not the expression, of reward timing in the visual cortex of awake, behaving animals. We then mimic reward timing in vitro by pairing white matter stimulation with muscarinic receptor activation at a fixed interval, and show that this protocol results in the prolongation of electrically-evoked spike train durations out to the conditioned interval. Together, these data suggest that (1) V1 possesses the circuitry and plasticity to support reward time prediction learning and (2) the cholinergic system serves as an important reinforcement signal which, in vivo, conveys to the cortex the outcome of behavior. PMID:23439124

  12. Serotonergic neurons signal reward and punishment on multiple timescales.

    PubMed

    Cohen, Jeremiah Y; Amoroso, Mackenzie W; Uchida, Naoshige

    2015-02-25

    Serotonin's function in the brain is unclear. One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks. We recorded the activity of dorsal raphe neurons while mice experienced a task in which rewards and punishments varied across blocks of trials. We 'tagged' serotonergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to light. We found three main features of serotonergic neuron activity: (1) a large fraction of serotonergic neurons modulated their tonic firing rates over the course of minutes during reward vs punishment blocks; (2) most were phasically excited by punishments; and (3) a subset was phasically excited by reward-predicting cues. By contrast, dopaminergic neurons did not show firing rate changes across blocks of trials. These results suggest that serotonergic neurons signal information about reward and punishment on multiple timescales.

  13. Speech prosody, reward, and the corticobulbar system: an integrative perspective.

    PubMed

    Vicario, Carmelo M

    2014-12-01

    Speech prosody is essential for verbal communication. In this commentary I provide an integrative overview, arguing that speech prosody is subserved by the same anatomical and neurochemical mechanisms involved in the processing of reward/affective outcomes.

  14. Bio-robots automatic navigation with electrical reward stimulation.

    PubMed

    Sun, Chao; Zhang, Xinlu; Zheng, Nenggan; Chen, Weidong; Zheng, Xiaoxiang

    2012-01-01

    Bio-robots that controlled by outer stimulation through brain computer interface (BCI) suffer from the dependence on realtime guidance of human operators. Current automatic navigation methods for bio-robots focus on the controlling rules to force animals to obey man-made commands, with animals' intelligence ignored. This paper proposes a new method to realize the automatic navigation for bio-robots with electrical micro-stimulation as real-time rewards. Due to the reward-seeking instinct and trial-and-error capability, bio-robot can be steered to keep walking along the right route with rewards and correct its direction spontaneously when rewards are deprived. In navigation experiments, rat-robots learn the controlling methods in short time. The results show that our method simplifies the controlling logic and realizes the automatic navigation for rat-robots successfully. Our work might have significant implication for the further development of bio-robots with hybrid intelligence.

  15. Caffeine in floral nectar enhances a pollinator's memory of reward.

    PubMed

    Wright, G A; Baker, D D; Palmer, M J; Stabler, D; Mustard, J A; Power, E F; Borland, A M; Stevenson, P C

    2013-03-08

    Plant defense compounds occur in floral nectar, but their ecological role is not well understood. We provide evidence that plant compounds pharmacologically alter pollinator behavior by enhancing their memory of reward. Honeybees rewarded with caffeine, which occurs naturally in nectar of Coffea and Citrus species, were three times as likely to remember a learned floral scent as were honeybees rewarded with sucrose alone. Caffeine potentiated responses of mushroom body neurons involved in olfactory learning and memory by acting as an adenosine receptor antagonist. Caffeine concentrations in nectar did not exceed the bees' bitter taste threshold, implying that pollinators impose selection for nectar that is pharmacologically active but not repellent. By using a drug to enhance memories of reward, plants secure pollinator fidelity and improve reproductive success.

  16. Motivating forces of human actions. Neuroimaging reward and social interaction.

    PubMed

    Walter, Henrik; Abler, Birgit; Ciaramidaro, Angela; Erk, Susanne

    2005-11-15

    In neuroeconomics, reward and social interaction are central concepts to understand what motivates human behaviour. Both concepts are investigated in humans using neuroimaging methods. In this paper, we provide an overview about these results and discuss their relevance for economic behaviour. For reward it has been shown that a system exists in humans that is involved in predicting rewards and thus guides behaviour, involving a circuit including the striatum, the orbitofrontal cortex and the amygdala. Recent studies on social interaction revealed a mentalizing system representing the mental states of others. A central part of this system is the medial prefrontal cortex, in particular the anterior paracingulate cortex. The reward as well as the mentalizing system is engaged in economic decision-making. We will discuss implications of this study for neuromarketing as well as general implications of these results that may help to provide deeper insights into the motivating forces of human behaviour.

  17. Reward Systems and Emergent Missions: Higher Education's Dilemma

    ERIC Educational Resources Information Center

    Lincoln, Yvonna S.; Guba, Egon G.

    1978-01-01

    After providing examples of how different reward systems impact on institutional and individual productivity, the authors present four strategies for changing the way promotion and tenure decisions are made in school of education. (IRT)

  18. Reward and reinforcement activity in the nucleus accumbens during learning

    PubMed Central

    Gale, John T.; Shields, Donald C.; Ishizawa, Yumiko; Eskandar, Emad N.

    2014-01-01

    The nucleus accumbens core (NAcc) has been implicated in learning associations between sensory cues and profitable motor responses. However, the precise mechanisms that underlie these functions remain unclear. We recorded single-neuron activity from the NAcc of primates trained to perform a visual-motor associative learning task. During learning, we found two distinct classes of NAcc neurons. The first class demonstrated progressive increases in firing rates at the go-cue, feedback/tone and reward epochs of the task, as novel associations were learned. This suggests that these neurons may play a role in the exploitation of rewarding behaviors. In contrast, the second class exhibited attenuated firing rates, but only at the reward epoch of the task. These findings suggest that some NAcc neurons play a role in reward-based reinforcement during learning. PMID:24765069

  19. Serotonin selectively modulates reward value in human decision-making

    PubMed Central

    Seymour, Ben; Daw, Nathaniel D.; Roiser, Jonathan P; Dayan, Peter; Dolan, Ray

    2017-01-01

    Establishing a function for the neuromodulator serotonin in human decision-making has proved remarkably difficult, because if its complex role in reward and punishment processing. In a novel choice task where actions led concurrently and independently to the stochastic delivery of both money and pain, we studied the impact of decreased brain serotonin induced by acute dietary tryptophan depletion. Depletion selectively impaired both behavioural and neural representations of reward outcome value, and hence the effective exchange rate by which rewards and punishments were compared. This effect was computationally and anatomically distinct from a separate effect on increasing outcome-independent choice perseveration. Our results provide evidence for a surprising role for serotonin in reward processing, while illustrating its complex and multifarious effects. PMID:22539845

  20. Homeostatic reinforcement learning for integrating reward collection and physiological stability.

    PubMed

    Keramati, Mehdi; Gutkin, Boris

    2014-12-02

    Efficient regulation of internal homeostasis and defending it against perturbations requires adaptive behavioral strategies. However, the computational principles mediating the interaction between homeostatic and associative learning processes remain undefined. Here we use a definition of primary rewards, as outcomes fulfilling physiological needs, to build a normative theory showing how learning motivated behaviors may be modulated by internal states. Within this framework, we mathematically prove that seeking rewards is equivalent to the fundamental objective of physiological stability, defining the notion of physiological rationality of behavior. We further suggest a formal basis for temporal discounting of rewards by showing that discounting motivates animals to follow the shortest path in the space of physiological variables toward the desired setpoint. We also explain how animals learn to act predictively to preclude prospective homeostatic challenges, and several other behavioral patterns. Finally, we suggest a computational role for interaction between hypothalamus and the brain reward system.

  1. Rewards in Nursing: The Case of Nurse Preceptors.

    ERIC Educational Resources Information Center

    Turnbull, Ellie

    1983-01-01

    Using nursing preceptorship programs as an example, the author illustrates how nursing administrators can develop and implement specific reward mechanisms that increase role satisfaction for preceptors and benefit both the service and the institution. (Author/SK)

  2. A spiking network model of decision making employing rewarded STDP.

    PubMed

    Skorheim, Steven; Lonjers, Peter; Bazhenov, Maxim

    2014-01-01

    Reward-modulated spike timing dependent plasticity (STDP) combines unsupervised STDP with a reinforcement signal that modulates synaptic changes. It was proposed as a learning rule capable of solving the distal reward problem in reinforcement learning. Nonetheless, performance and limitations of this learning mechanism have yet to be tested for its ability to solve biological problems. In our work, rewarded STDP was implemented to model foraging behavior in a simulated environment. Over the course of training the network of spiking neurons developed the capability of producing highly successful decision-making. The network performance remained stable even after significant perturbations of synaptic structure. Rewarded STDP alone was insufficient to learn effective decision making due to the difficulty maintaining homeostatic equilibrium of synaptic weights and the development of local performance maxima. Our study predicts that successful learning requires stabilizing mechanisms that allow neurons to balance their input and output synapses as well as synaptic noise.

  3. Food reward in the absence of taste receptor signaling.

    PubMed

    de Araujo, Ivan E; Oliveira-Maia, Albino J; Sotnikova, Tatyana D; Gainetdinov, Raul R; Caron, Marc G; Nicolelis, Miguel A L; Simon, Sidney A

    2008-03-27

    Food palatability and hedonic value play central roles in nutrient intake. However, postingestive effects can influence food preferences independently of palatability, although the neurobiological bases of such mechanisms remain poorly understood. Of central interest is whether the same brain reward circuitry that is responsive to palatable rewards also encodes metabolic value independently of taste signaling. Here we show that trpm5-/- mice, which lack the cellular machinery required for sweet taste transduction, can develop a robust preference for sucrose solutions based solely on caloric content. Sucrose intake induced dopamine release in the ventral striatum of these sweet-blind mice, a pattern usually associated with receipt of palatable rewards. Furthermore, single neurons in this same ventral striatal region showed increased sensitivity to caloric intake even in the absence of gustatory inputs. Our findings suggest that calorie-rich nutrients can directly influence brain reward circuits that control food intake independently of palatability or functional taste transduction.

  4. The effects of cooperative and individualistic reward on intrinsic motivation.

    PubMed

    Hom, H L; Berger, M; Duncan, M K; Miller, A; Blevin, A

    1994-03-01

    The effects of cooperative versus individualistic reward on students' intrinsic motivation were investigated. The controlling aspects of extrinsic reward may be heightened or produce greater ego threat in the individualistic situation when compared with a group situation. We predicted that students in the cooperative social situation would show higher levels of intrinsic motivation. Fifth-grade students from existing cooperative groups were assigned randomly to receive a tangible reward based on either cooperative or individualistic achievement for completing pattern block designs. Cooperation affected intrinsic motivation positively. Students in the cooperative dyad solved the block designs more quickly, interacted positively, and viewed the task as easier than did those in the individualistic situation, and they reported that their peers were helpful. There was little evidence that the controlling functions of reward or ego-threat were factors in producing the outcome. Some evidence supporting the importance of the social nature of cooperation was provided.

  5. Rewards of entering podiatric medicine and attitudes toward older adults.

    PubMed

    Chumbler, N R; Robbins, J M; Poplawski, M E

    1996-06-01

    This study examined the relationships between social and demographic characteristics (ie, gender, race, year in school, desired residency choice, and socioeconomic background), motivations for entering the profession of podiatric medicine (extrinsic and intrinsic rewards), and negative attitudes toward treating elderly patients. The study used ordinary least squares multiple regression models to analyze data from a random, national sample of 448 podiatric medical students. In particular, the ordinary least squares models were developed to determine the independent effect of intrinsic and extrinsic rewards on negative attitudes toward treating elderly patients. Consistent with the study hypotheses, after adjusting for social and demographic characteristics, the study found extrinsic rewards to have strong positive relationships with negative attitudes toward treating elderly patients, and intrinsic rewards to have strong negative relationships with negative attitudes toward treating elderly patients. The authors discussed the implications of the findings for podiatric physicians and educators training podiatric medical students.

  6. Mind matters: placebo enhances reward learning in Parkinson's disease.

    PubMed

    Schmidt, Liane; Braun, Erin Kendall; Wager, Tor D; Shohamy, Daphna

    2014-12-01

    Expectations have a powerful influence on how we experience the world. Neurobiological and computational models of learning suggest that dopamine is crucial for shaping expectations of reward and that expectations alone may influence dopamine levels. However, because expectations and reinforcers are typically manipulated together, the role of expectations per se has remained unclear. We separated these two factors using a placebo dopaminergic manipulation in individuals with Parkinson's disease. We combined a reward learning task with functional magnetic resonance imaging to test how expectations of dopamine release modulate learning-related activity in the brain. We found that the mere expectation of dopamine release enhanced reward learning and modulated learning-related signals in the striatum and the ventromedial prefrontal cortex. These effects were selective to learning from reward: neither medication nor placebo had an effect on learning to avoid monetary loss. These findings suggest a neurobiological mechanism by which expectations shape learning and affect.

  7. "Small Steps, Big Rewards": You Can Prevent Type 2 Diabetes

    MedlinePlus

    ... Steps, Big Rewards": You Can Prevent Type 2 Diabetes Past Issues / Winter 2008 Table of Contents For ... million Americans are at risk for type 2 diabetes." "Fifty four million Americans are at risk for ...

  8. Reward Motivation Enhances Task Coding in Frontoparietal Cortex.

    PubMed

    Etzel, Joset A; Cole, Michael W; Zacks, Jeffrey M; Kay, Kendrick N; Braver, Todd S

    2016-04-01

    Reward motivation often enhances task performance, but the neural mechanisms underlying such cognitive enhancement remain unclear. Here, we used a multivariate pattern analysis (MVPA) approach to test the hypothesis that motivation-related enhancement of cognitive control results from improved encoding and representation of task set information. Participants underwent two fMRI sessions of cued task switching, the first under baseline conditions, and the second with randomly intermixed reward incentive and no-incentive trials. Information about the upcoming task could be successfully decoded from cue-related activation patterns in a set of frontoparietal regions typically associated with task control. More critically, MVPA classifiers trained on the baseline session had significantly higher decoding accuracy on incentive than non-incentive trials, with decoding improvement mediating reward-related enhancement of behavioral performance. These results strongly support the hypothesis that reward motivation enhances cognitive control, by improving the discriminability of task-relevant information coded and maintained in frontoparietal brain regions.

  9. The Influence of Palatable Diets in Reward System Activation: A Mini Review

    PubMed Central

    de Macedo, Isabel Cristina; de Freitas, Joice Soares; da Silva Torres, Iraci Lucena

    2016-01-01

    The changes in eating patterns that have occurred in recent decades are an important cause of obesity. Food intake and energy expenditure are controlled by a complex neural system involving the hypothalamic centers and peripheral satiety system (gastrointestinal and pancreatic hormones). Highly palatable and caloric food disrupts appetite regulation; however, palatable foods induce pleasure and reward. The cafeteria diet is such a palatable diet and has been shown consistently to increase body weight and induce hyperplasia in animal obesity models. Moreover, palatable high-fat foods (such as those of the cafeteria diet) can induce addiction-like deficits in brain reward function and are considered to be an important source of motivation that might drive overeating and contribute to the development of obesity. The mechanism of neural adaptation triggered by palatable foods is similar to those that have been reported for nondrug addictions and long-term drug use. Thus, this review attempts to describe the potential mechanisms that might lead to highly palatable diets, such as the cafeteria diet, triggering addiction, or compulsion through the reward system. PMID:27087806

  10. The Influence of Palatable Diets in Reward System Activation: A Mini Review.

    PubMed

    de Macedo, Isabel Cristina; de Freitas, Joice Soares; da Silva Torres, Iraci Lucena

    2016-01-01

    The changes in eating patterns that have occurred in recent decades are an important cause of obesity. Food intake and energy expenditure are controlled by a complex neural system involving the hypothalamic centers and peripheral satiety system (gastrointestinal and pancreatic hormones). Highly palatable and caloric food disrupts appetite regulation; however, palatable foods induce pleasure and reward. The cafeteria diet is such a palatable diet and has been shown consistently to increase body weight and induce hyperplasia in animal obesity models. Moreover, palatable high-fat foods (such as those of the cafeteria diet) can induce addiction-like deficits in brain reward function and are considered to be an important source of motivation that might drive overeating and contribute to the development of obesity. The mechanism of neural adaptation triggered by palatable foods is similar to those that have been reported for nondrug addictions and long-term drug use. Thus, this review attempts to describe the potential mechanisms that might lead to highly palatable diets, such as the cafeteria diet, triggering addiction, or compulsion through the reward system.

  11. Effect of yohimbine on reinstatement of operant responding in rats is dependent on cue contingency but not food reward history

    PubMed Central

    Chen, Yu-Wei; Fiscella, Kimberly A.; Bacharach, Samuel Z.; Tanda, Gianluigi; Shaham, Yavin; Calu, Donna J.

    2014-01-01

    Yohimbine is an alpha-2 adrenoceptor antagonist that has been used in numerous studies as a pharmacological stressor in rodents, monkeys, and humans. Recently, yohimbine has become the most common stress manipulation in studies on reinstatement of drug and food seeking. However, the wide range of conditions under which yohimbine promotes reward seeking is significantly greater than that of stressors like intermittent footshock. Here we addressed two fundamental questions regarding yohimbine’s effect on reinstatement of reward seeking: (1) whether the drug’s effect on operant responding is dependent on previous reward history or cue contingency, and (2) whether yohimbine is aversive or rewarding under conditions typically used in reinstatement studies. We also used in vivo microdialysis to determine yohimbine’s effect on dopamine levels in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We found that the magnitude of yohimbine-induced (0.5, 1.0, 2.0 mg/kg) operant responding during the reinstatement tests was critically dependent on the contingency between lever-pressing and discrete tone-light cue delivery but not the previous history with food reward during training. We also found that yohimbine (2 mg/kg) did not cause conditioned place aversion. Finally, we found that yohimbine modestly increased dopamine levels in mPFC but not NAc. Results suggest that yohimbine’s effects on operant responding in reinstatement studies are likely independent of the history of contingent self-administration of food or drug rewards and may not be related to the commonly assumed stress-like effects of yohimbine. PMID:25065697

  12. Effect of yohimbine on reinstatement of operant responding in rats is dependent on cue contingency but not food reward history.

    PubMed

    Chen, Yu-Wei; Fiscella, Kimberly A; Bacharach, Samuel Z; Tanda, Gianluigi; Shaham, Yavin; Calu, Donna J

    2015-07-01

    Yohimbine is an alpha-2 adrenoceptor antagonist that has been used in numerous studies as a pharmacological stressor in rodents, monkeys and humans. Recently, yohimbine has become the most common stress manipulation in studies on reinstatement of drug and food seeking. However, the wide range of conditions under which yohimbine promotes reward seeking is significantly greater than that of stressors like intermittent footshock. Here, we addressed two fundamental questions regarding yohimbine's effect on reinstatement of reward seeking: (1) whether the drug's effect on operant responding is dependent on previous reward history or cue contingency, and (2) whether yohimbine is aversive or rewarding under conditions typically used in reinstatement studies. We also used in vivo microdialysis to determine yohimbine's effect on dopamine levels in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We found that the magnitude of yohimbine-induced (0.5, 1.0, 2.0 mg/kg) operant responding during the reinstatement tests was critically dependent on the contingency between lever pressing and discrete tone-light cue delivery but not the previous history with food reward during training. We also found that yohimbine (2 mg/kg) did not cause conditioned place aversion. Finally, we found that yohimbine modestly increased dopamine levels in mPFC but not NAc. Results suggest that yohimbine's effects on operant responding in reinstatement studies are likely independent of the history of contingent self-administration of food or drug rewards and may not be related to the commonly assumed stress-like effects of yohimbine.

  13. fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder.

    PubMed

    Smoski, Moria J; Felder, Jennifer; Bizzell, Joshua; Green, Steven R; Ernst, Monique; Lynch, Thomas R; Dichter, Gabriel S

    2009-11-01

    The purpose of the present investigation was to evaluate reward processing in unipolar major depressive disorder (MDD). Specifically, we investigated whether adults with MDD demonstrated hyporesponsivity in striatal brain regions and/or hyperresponsivity in cortical brain regions involved in conflict monitoring using a Wheel of Fortune task designed to probe responses during reward selection, reward anticipation, and reward feedback. Functional magnetic resonance imaging (fMRI) data indicated that the MDD group was characterized by reduced activation of striatal reward regions during reward selection, reward anticipation, and reward feedback, supporting previous data indicating hyporesponsivity of reward systems in MDD. Support was not found for hyperresponsivity of cognitive control regions during reward selection or reward anticipation. Instead, MDD participants showed hyperresponsivity in orbitofrontal cortex, a region associated with assessment of risk and reward, during reward selection, as well as decreased activation of the middle frontal gyrus and the rostral cingulate gyrus during reward selection and anticipation. Finally, depression severity was predicted by activation in bilateral midfrontal gyrus during reward selection. Results indicate that MDD is characterized by striatal hyporesponsivity, and that future studies of MDD treatments that seek to improve responses to rewarding stimuli should assess striatal functioning.

  14. Intrinsic Motivation and Rewards: What Sustains Young Children's Engagement with Text?

    ERIC Educational Resources Information Center

    Marinak, Barbara A.; Gambrell, Linda B.

    2008-01-01

    This study investigated the effects of reward proximity and choice of reward on the reading motivation of third-grade students as measured by indicators of task persistence. The major finding from this study was that students who were given a book as a reward and students who received no reward were more motivated to engage in subsequent reading…

  15. Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward.

    PubMed

    Yokel, R A; Wise, R A

    1975-02-14

    Low and high doses of a dopamine blocking agent had effects on lever pressing for intravenous amphetamine reward which resembled the effects of reward reduction and reward termination, respectively. Noradrenaline blockade had no such effects. A role in central mediation of reward perception is suggested for dopamine but not for noradrenaline.

  16. A new "loyalty rewards" program in health care customer relationships.

    PubMed

    Macstravic, Scott

    2006-01-01

    "Loyalty rewards" in sponsored DM and HRM programs can apply to both providers and consumers. Physicians and hospitals can be paid to "loyally" adhere to payers' guidelines for managing diseases and risks. Many payer and their outsourced vendor programs include significant efforts to create collaborations between payer and provider, rather than relying on unilateral efforts. And growing numbers are rewarding providers for their efforts and results achieved.

  17. Neural Activity in the Ventral Pallidum Encodes Variation in the Incentive Value of a Reward Cue

    PubMed Central

    Meyer, Paul J.; Ferguson, Lindsay M.; Robinson, Terry E.; Aldridge, J. Wayne

    2016-01-01

    There is considerable individual variation in the extent to which reward cues are attributed with incentive salience. For example, a food-predictive conditioned stimulus (CS; an illuminated lever) becomes attractive, eliciting approach toward it only in some rats (“sign trackers,” STs), whereas others (“goal trackers,” GTs) approach the food cup during the CS period. The purpose of this study was to determine how individual differences in Pavlovian approach responses are represented in neural firing patterns in the major output structure of the mesolimbic system, the ventral pallidum (VP). Single-unit in vivo electrophysiology was used to record neural activity in the caudal VP during the performance of ST and GT conditioned responses. All rats showed neural responses to both cue onset and reward delivery but, during the CS period, STs showed greater neural activity than GTs both in terms of the percentage of responsive neurons and the magnitude of the change in neural activity. Furthermore, neural activity was positively correlated with the degree of attraction to the cue. Given that the CS had equal predictive value in STs and GTs, we conclude that neural activity in the VP largely reflects the degree to which the CS was attributed with incentive salience. SIGNIFICANCE STATEMENT Cues associated with reward can acquire motivational properties (i.e., incentive salience) that cause them to have a powerful influence on desire and motivated behavior. There are individual differences in sensitivity to reward-paired cues, with some individuals attaching greater motivational value to cues than others. Here, we investigated the neural activity associated with these individual differences in incentive salience. We found that cue-evoked neural firing in the ventral pallidum (VP) reflected the strength of incentive motivation, with the greatest neural responses occurring in individuals that demonstrated the strongest attraction to the cue. This suggests that the VP

  18. Neuron as a reward-modulated combinatorial switch and a model of learning behavior.

    PubMed

    Rvachev, Marat M

    2013-10-01

    This paper proposes a neuronal circuitry layout and synaptic plasticity principles that allow the (pyramidal) neuron to act as a "combinatorial switch". Namely, the neuron learns to be more prone to generate spikes given those combinations of firing input neurons for which a previous spiking of the neuron had been followed by a positive global reward signal. The reward signal may be mediated by certain modulatory hormones or neurotransmitters, e.g., the dopamine. More generally, a trial-and-error learning paradigm is suggested in which a global reward signal triggers long-term enhancement or weakening of a neuron's spiking response to the preceding neuronal input firing pattern. Thus, rewards provide a feedback pathway that informs neurons whether their spiking was beneficial or detrimental for a particular input combination. The neuron's ability to discern specific combinations of firing input neurons is achieved through a random or predetermined spatial distribution of input synapses on dendrites that creates synaptic clusters that represent various permutations of input neurons. The corresponding dendritic segments, or the enclosed individual spines, are capable of being particularly excited, due to local sigmoidal thresholding involving voltage-gated channel conductances, if the segment's excitatory and absence of inhibitory inputs are temporally coincident. Such nonlinear excitation corresponds to a particular firing combination of input neurons, and it is posited that the excitation strength encodes the combinatorial memory and is regulated by long-term plasticity mechanisms. It is also suggested that the spine calcium influx that may result from the spatiotemporal synaptic input coincidence may cause the spine head actin filaments to undergo mechanical (muscle-like) contraction, with the ensuing cytoskeletal deformation transmitted to the axon initial segment where it may modulate the global neuron firing threshold. The tasks of pattern classification and

  19. It's all about money: oral contraception alters neural reward processing.

    PubMed

    Bonenberger, Martina; Groschwitz, Rebecca C; Kumpfmueller, Daniela; Groen, Georg; Plener, Paul L; Abler, Birgit

    2013-12-04

    Mating preferences in phases of the natural menstrual cycle with a low probability to conceive have been associated with lower interest in characteristics promising genetic benefits but increased search for safety and future security. We hypothesized that this effect would also be evident under oral contraception and may therefore alter neural processing of monetary rewards as a proxy for potential safety. Our aim was to assess the activation of reward-related brain areas using a monetary incentive task in women with functional MRI (fMRI). We compared fMRI activation of 12 young women taking oral contraceptives with 12 women with a natural hormonal cycle in their follicular phase during the expectation of monetary rewards. Women under hormonal contraception who have already shown decreased anterior insula activation upon erotic stimulation in a previous study of the same sample now showed enhanced activation during monetary reward expectation in the anterior insula/inferior lateral prefrontal cortex (t=2.84; P<0.05) relative to young normal cycling women in the follicular phase. Our finding supports the notion that the switch in mating preferences related to different hormonal states in women is mirrored by a switch in the stimulus-dependent excitability of reward-related brain regions. Beyond highlighting hormonal effects on reward processing, our data underline the importance of monitoring hormonal states in fMRI research in women.

  20. Frontostriatal response to set switching is moderated by reward sensitivity

    PubMed Central

    Garbin, Gabriele; Sanjuán, Ana; Forn, Cristina; Barrós-Loscertales, Alfonso; Bustamante, Juan Carlos; Rodríguez-Pujadas, Aina; Belloch, Vicente; Parcet, Maria Antònia

    2012-01-01

    The reinforcement sensitivity theory (RST) relates individual differences in reward sensitivity to the activation of the behavioral approach system (BAS). Dopamine-related brain structures have been repeatedly associated with reward processing, but also with cognitive processes such as task switching. In the present study, we examined the association between reward sensitivity and the event-related fMRI BOLD response with set switching in 31 males. As expected, the right inferior frontal cortex (rIFG) and the striatum (i.e. the left putamen) were involved in set-switching activity for the overall sample. Interindividual differences in Gray's reward sensitivity were related to stronger activity in the rIFG and the ventral striatum. Thus, trait reward sensitivity contributed to the modulation of brain responsiveness in set-switching tasks. Having considered previous research, we propose that higher BAS activity is associated with a stronger reward to process a better implementation of goal-directed tasks and the diminished processing of secondary cues. PMID:21737433

  1. Object-finding skill created by repeated reward experience

    PubMed Central

    Ghazizadeh, Ali; Griggs, Whitney; Hikosaka, Okihide

    2016-01-01

    For most animals, survival depends on rapid detection of rewarding objects, but search for an object surrounded by many others is known to be difficult and time consuming. However, there is neuronal evidence for robust and rapid differentiation of objects based on their reward history in primates (Hikosaka, Kim, Yasuda, & Yamamoto, 2014). We hypothesized that such robust coding should support efficient search for high-value objects, similar to a pop-out mechanism. To test this hypothesis, we let subjects (n = 4, macaque monkeys) view a large number of complex objects with consistently biased rewards with variable training durations (1, 5, or 30 + days). Following training, subjects searched for a high-value object (Good) among a variable number of low-value objects (Bad). Consistent with our hypothesis, we found that Good objects were accurately and quickly targeted, often by a single and direct saccade with a very short latency (<200 ms). The dependence of search times on display size reduced significantly with longer reward training, giving rise to a more efficient search (40 ms/item to 16 ms/item). This object-finding skill showed a large capacity for value-biased objects and was maintained in the long-term memory with no interference from reward learning with other objects. Such object-finding skill, and in particular its large capacity and long term retention, would be crucial for maximizing rewards and biological fitness throughout life where many objects are experienced continuously and/or intermittently. PMID:27564993

  2. 5-HT receptors and reward-related behaviour: a review.

    PubMed

    Hayes, Dave J; Greenshaw, Andrew J

    2011-05-01

    The brain's serotonin (5-HT) system is key in the regulation of reward-related behaviours, from eating and drinking to sexual activity. The complexity of studying this system is due, in part, to the fact that 5-HT acts at many receptor subtypes throughout the brain. The recent development of drugs with greater selectivity for individual receptor subtypes has allowed for rapid advancements in our understanding of this system. Use of these drugs in combination with animal models entailing selective reward measures (i.e. intracranial self-stimulation, drug self-administration, conditioned place preference) have resulted in a greater understanding of the pharmacology of reward-related processing and behaviour (particularly regarding drugs of abuse). The putative roles of each 5-HT receptor subtype in the pharmacology of reward are outlined and discussed here. It is concluded that the actions of 5-HT in reward are receptor subtype-dependent (and thus should not be generalized) and that all studied subtypes appear to have a unique profile which is determined by content (e.g. receptor function, localization - both throughout the brain and within the synapse) and context (e.g. type of behavioural paradigm, type of drug). Given evidence of altered reward-related processing and serotonergic function in numerous neuropsychiatric disorders, such as depression, schizophrenia, and addiction, a clearer understanding of the role of 5-HT receptor subtypes in this context may lead to improved drug development and therapeutic approaches.

  3. Reward-based contextual learning supported by anterior cingulate cortex.

    PubMed

    Umemoto, Akina; HajiHosseini, Azadeh; Yates, Michael E; Holroyd, Clay B

    2017-02-24

    The anterior cingulate cortex (ACC) is commonly associated with cognitive control and decision making, but its specific function is highly debated. To explore a recent theory that the ACC learns the reward values of task contexts (Holroyd & McClure in Psychological Review, 122, 54-83, 2015; Holroyd & Yeung in Trends in Cognitive Sciences, 16, 122-128, 2012), we recorded the event-related brain potentials (ERPs) from participants as they played a novel gambling task. The participants were first required to select from among three games in one "virtual casino," and subsequently they were required to select from among three different games in a different virtual casino; unbeknownst to them, the payoffs for the games were higher in one casino than in the other. Analysis of the reward positivity, an ERP component believed to reflect reward-related signals carried to the ACC by the midbrain dopamine system, revealed that the ACC is sensitive to differences in the reward values associated with both the casinos and the games inside the casinos, indicating that participants learned the values of the contexts in which rewards were delivered. These results highlight the importance of the ACC in learning the reward values of task contexts in order to guide action selection.

  4. Revealing the paradox of drug reward in human evolution

    PubMed Central

    Sullivan, Roger J; Hagen, Edward H; Hammerstein, Peter

    2008-01-01

    Neurobiological models of drug abuse propose that drug use is initiated and maintained by rewarding feedback mechanisms. However, the most commonly used drugs are plant neurotoxins that evolved to punish, not reward, consumption by animal herbivores. Reward models therefore implicitly assume an evolutionary mismatch between recent drug-profligate environments and a relatively drug-free past in which a reward centre, incidentally vulnerable to neurotoxins, could evolve. By contrast, emerging insights from plant evolutionary ecology and the genetics of hepatic enzymes, particularly cytochrome P450, indicate that animal and hominid taxa have been exposed to plant toxins throughout their evolution. Specifically, evidence of conserved function, stabilizing selection, and population-specific selection of human cytochrome P450 genes indicate recent evolutionary exposure to plant toxins, including those that affect animal nervous systems. Thus, the human propensity to seek out and consume plant neurotoxins is a paradox with far-reaching implications for current drug-reward theory. We sketch some potential resolutions of the paradox, including the possibility that humans may have evolved to counter-exploit plant neurotoxins. Resolving the paradox of drug reward will require a synthesis of ecological and neurobiological perspectives of drug seeking and use. PMID:18353749

  5. CRF1 receptor-deficiency increases cocaine reward.

    PubMed

    Contarino, Angelo; Kitchener, Pierre; Vallée, Monique; Papaleo, Francesco; Piazza, Pier-Vincenzo

    2017-01-27

    Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF1 receptor-deficient (CRF1-/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF1-/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF1-/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF1-/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF1-/- mice by exogenous corticosterone does not affect CRF1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF1 receptor in cocaine reward, independently of the closely related HPA axis activity.

  6. Altered Social Reward and Attention in Anorexia Nervosa

    PubMed Central

    Watson, Karli K.; Werling, Donna M.; Zucker, Nancy L.; Platt, Michael L.

    2010-01-01

    Dysfunctional social reward and social attention are present in a variety of neuropsychiatric disorders including autism, schizophrenia, and social anxiety. Here we show that similar social reward and attention dysfunction are present in anorexia nervosa (AN), a disorder defined by avoidance of food and extreme weight loss. We measured the implicit reward value of social stimuli for female participants with (n = 11) and without (n = 11) AN using an econometric choice task and also tracked gaze patterns during free viewing of images of female faces and bodies. As predicted, the reward value of viewing bodies varied inversely with observed body weight for women with anorexia but not contro