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  • 1
    Publication Date: 2010-12-15
    Description: Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, becoming attractive and desirable incentive stimuli. However, whether a cue acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Thus, individuals vary in the degree to which cues bias choice and potentially promote maladaptive behaviour. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of stimulus-reward learning in which incentive salience is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behaviour. This work provides insight into the neurobiology of a form of stimulus-reward learning that confers increased susceptibility to disorders of impulse control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058375/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058375/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flagel, Shelly B -- Clark, Jeremy J -- Robinson, Terry E -- Mayo, Leah -- Czuj, Alayna -- Willuhn, Ingo -- Akers, Christina A -- Clinton, Sarah M -- Phillips, Paul E M -- Akil, Huda -- 5P01-DA021633-02/DA/NIDA NIH HHS/ -- F32-DA24540/DA/NIDA NIH HHS/ -- P01 DA021633/DA/NIDA NIH HHS/ -- P01 DA021633-02/DA/NIDA NIH HHS/ -- R00 MH085859/MH/NIMH NIH HHS/ -- R00 MH085859-02/MH/NIMH NIH HHS/ -- R01 DA027858/DA/NIDA NIH HHS/ -- R01 MH079292/MH/NIMH NIH HHS/ -- R01-DA027858/DA/NIDA NIH HHS/ -- R01-MH079292/MH/NIMH NIH HHS/ -- R37-DA04294/DA/NIDA NIH HHS/ -- T32-DA07278/DA/NIDA NIH HHS/ -- England -- Nature. 2011 Jan 6;469(7328):53-7. doi: 10.1038/nature09588. Epub 2010 Dec 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Behavioral Neuroscience Institute, University of Michigan, Michigan, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21150898" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conditioning, Classical/drug effects/physiology ; *Cues ; Disruptive, Impulse Control, and Conduct Disorders/physiopathology ; Dopamine/*metabolism ; Dopamine Antagonists/pharmacology ; Flupenthixol/pharmacology ; Food ; Learning/drug effects/*physiology ; Male ; Microelectrodes ; *Models, Neurological ; Motivation/drug effects ; Nucleus Accumbens/metabolism ; Phenotype ; Probability ; Rats ; Rats, Sprague-Dawley ; *Reward ; Signal Transduction ; Synaptic Transmission
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-08-06
    Description: Predictions about future rewarding events have a powerful influence on behaviour. The phasic spike activity of dopamine-containing neurons, and corresponding dopamine transients in the striatum, are thought to underlie these predictions, encoding positive and negative reward prediction errors. However, many behaviours are directed towards distant goals, for which transient signals may fail to provide sustained drive. Here we report an extended mode of reward-predictive dopamine signalling in the striatum that emerged as rats moved towards distant goals. These dopamine signals, which were detected with fast-scan cyclic voltammetry (FSCV), gradually increased or--in rare instances--decreased as the animals navigated mazes to reach remote rewards, rather than having phasic or steady tonic profiles. These dopamine increases (ramps) scaled flexibly with both the distance and size of the rewards. During learning, these dopamine signals showed spatial preferences for goals in different locations and readily changed in magnitude to reflect changing values of the distant rewards. Such prolonged dopamine signalling could provide sustained motivational drive, a control mechanism that may be important for normal behaviour and that can be impaired in a range of neurologic and neuropsychiatric disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927840/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927840/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howe, Mark W -- Tierney, Patrick L -- Sandberg, Stefan G -- Phillips, Paul E M -- Graybiel, Ann M -- R01 AG044839/AG/NIA NIH HHS/ -- R01 DA027858/DA/NIDA NIH HHS/ -- R01 MH060379/MH/NIMH NIH HHS/ -- R01 MH079292/MH/NIMH NIH HHS/ -- England -- Nature. 2013 Aug 29;500(7464):575-9. doi: 10.1038/nature12475. Epub 2013 Aug 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23913271" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Dopamine/*metabolism ; Dopaminergic Neurons/metabolism ; Goals ; Male ; Maze Learning ; Models, Neurological ; Models, Psychological ; Motivation ; Neostriatum/cytology/*metabolism ; Rats ; Rats, Long-Evans ; *Reward ; *Signal Transduction ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2012-09-21
    Description: Stressors motivate an array of adaptive responses ranging from 'fight or flight' to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF's capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475726/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475726/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lemos, Julia C -- Wanat, Matthew J -- Smith, Jeffrey S -- Reyes, Beverly A S -- Hollon, Nick G -- Van Bockstaele, Elisabeth J -- Chavkin, Charles -- Phillips, Paul E M -- F31 MH086269/MH/NIMH NIH HHS/ -- F31-MH086269/MH/NIMH NIH HHS/ -- F32-DA026273/DA/NIDA NIH HHS/ -- K05 DA020570/DA/NIDA NIH HHS/ -- R01 DA009082/DA/NIDA NIH HHS/ -- R01 DA016782/DA/NIDA NIH HHS/ -- R01 DA030074/DA/NIDA NIH HHS/ -- R01 MH079292/MH/NIMH NIH HHS/ -- R01-DA009082/DA/NIDA NIH HHS/ -- R01-DA016782/DA/NIDA NIH HHS/ -- R01-DA030074/DA/NIDA NIH HHS/ -- R01-MH079292/MH/NIMH NIH HHS/ -- England -- Nature. 2012 Oct 18;490(7420):402-6. doi: 10.1038/nature11436. Epub 2012 Sep 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22992525" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Appetitive Behavior/drug effects/*physiology ; Avoidance Learning/drug effects/*physiology ; Corticotropin-Releasing Hormone/*metabolism/pharmacology ; Dopamine/metabolism/secretion ; Male ; Mice ; Mice, Inbred C57BL ; Nucleus Accumbens/*metabolism/physiopathology ; Receptors, Corticotropin-Releasing Hormone/agonists/antagonists & ; inhibitors/deficiency/metabolism ; Signal Transduction/drug effects ; Stress, Psychological/*metabolism/physiopathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2016-03-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hollon, Nick G -- Phillips, Paul E M -- England -- Nature. 2016 Mar 31;531(7596):588-9. doi: 10.1038/nature17314. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Department of Psychiatry &Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007851" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Decision Making ; Humans ; Male ; Neurons/*metabolism ; Nucleus Accumbens/*cytology/*metabolism ; Receptors, Dopamine D2/*metabolism ; *Risk Management
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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