Avoidance of harm and anxiety: A role for the nucleus accumbens

Levita, Liat; Hoskin, Robert E.; Christou-Champi, Spyros

doi:10.1016/j.neuroimage.2012.04.059

Cited by 124 publications

(106 citation statements)

References 95 publications

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“…Our results showed that negative emotion induced by the unpleasant pictures similarly induced avoidance behavior through common neural systems with other aversive stimuli. In addition, our results are consistent with Levita et al (2012), who reported that the BOLD responses from the ventral striatum are higher in active avoidance conditions compared with passive avoidance conditions. A series of fMRI studies reported that the BOLD responses in striatum are dominated by action requirements (e.g., go vs. no go) rather than by valence, in accord with the view that dopamine has a role in modulating vigor or motivation for actions independent of valence (Guitart-Masip et al 2011.…”

Section: Discussionsupporting

confidence: 93%

Neural basis of decision making guided by emotional outcomes

Katahira

Matsuda

Fujimura

et al. 2015

Journal of Neurophysiology

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Emotional events resulting from a choice influence an individual's subsequent decision making. Although the relationship between emotion and decision making has been widely discussed, previous studies have mainly investigated decision outcomes that can easily be mapped to reward and punishment, including monetary gain/loss, gustatory stimuli, and pain. These studies regard emotion as a modulator of decision making that can be made rationally in the absence of emotions. In our daily lives, however, we often encounter various emotional events that affect decisions by themselves, and mapping the events to a reward or punishment is often not straightforward. In this study, we investigated the neural substrates of how such emotional decision outcomes affect subsequent decision making. By using functional magnetic resonance imaging (fMRI), we measured brain activities of humans during a stochastic decision-making task in which various emotional pictures were presented as decision outcomes. We found that pleasant pictures differentially activated the midbrain, fusiform gyrus, and parahippocampal gyrus, whereas unpleasant pictures differentially activated the ventral striatum, compared with neutral pictures. We assumed that the emotional decision outcomes affect the subsequent decision by updating the value of the options, a process modeled by reinforcement learning models, and that the brain regions representing the prediction error that drives the reinforcement learning are involved in guiding subsequent decisions. We found that some regions of the striatum and the insula were separately correlated

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Section: Discussionsupporting

confidence: 93%

Neural basis of decision making guided by emotional outcomes

Katahira

Matsuda

Fujimura

et al. 2015

Journal of Neurophysiology

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“…Recent fMRI data have supported the idea that the NAc is involved in not only the reward-based action-contingencies but also the etiology and maintenance of aberrant avoidance behaviors in anxiety disorders [39] . The microinjection of corticotropin-releasing factor into the NAc shell induced anxiety-like behaviors in an elevated plus maze and open field, which indicates the role of the NAc shell in anxiety [40] .…”

Section: Discussionmentioning

confidence: 93%

Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats

et al. 2014

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Aim: Glutamatergic neurotransmission in the nucleus accumbens (NAc) is crucial for the relapse to heroin seeking. The aim of this study was to determine whether mGluR5 in the NAc core or shell involved in heroin seeking behavior in rats. Methods: Male SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks. The selective mGluR5 antagonist 2-methyl-6-phenylethynyl-pyridine (MPEP, 5, 15 and 50 nmol per side) was then microinjected into the NAc core or shell 10 min before a heroin-seeking test induced by context, cues or heroin priming. Results: Microinjection of MPEP into the NAc shell dose-dependently decreased the heroin seeking induced by context, cues or heroin priming. In contrast, microinjection of MPEP into the NAc core did not alter the heroin seeking induced by cues or heroin priming. In addition, microinjection with MPEP (15 nmol per side) in the NAc shell reversed both the percentage of open arms entries (OE%) and the percentage of time spent in open arms (OT%) after heroin withdrawal. Microinjection of MPEP (50 nmol per side) in the striatum as a control location did not affect the heroin seeking behavior. Microinjection of MPEP in the 3 locations did not change the locomotion activities. Conclusion: Blockade of mGluR5 in NAc shell in rats specifically suppresses the relapse to heroin-seeking and anxiety-like behavior, suggesting that mGluR5 antagonists may be a potential candidate for the therapy of heroin addiction.Keywords: heroin; addiction; relapse; mGluR5; MPEP; the nucleus accumbens; striatum Acta Pharmacologica Sinica (2014Sinica ( ) 35: 1485Sinica ( -1492 doi: 10.1038/aps.2014 published online Nov 17 2014 Original Article IntroductionRelapse is the most important manifestation of heroin addiction following prolonged periods of abstinence [1] . Relapse arises from intense craving that can be triggered by a single drug-taking experience or exposure to an environmental stimulus [2] . The pre-clinical literature indicates that longterm drug-induced alterations in glutamatergic transmission within the NAc may underlie relapse to drug-seeking behavior following the re-exposure to drugs and drugassociated stimuli during abstinence of the drug [3,4] . Type 5 metabotropic glutamate receptor (mGluR5) as a postsynaptic element is abundantly present throughout in the NAc, where it is positively coupled to NMDA receptor function and mediates various forms of synaptic plasticity [5,6] . The deletion of mGluR5 results in marked deficits in responding to the reinforcing and locomotor stimulating effects of cocaine [7] . Furthermore, the administration of the noncompetitive selective mGluR5 antagonist 2-methyl-6 (phenyethynyl) pyridine (MPEP) decreased the self-administration and/or relapse of nicotine [8,9] , cocaine [10,11] , ethanol [12][13][14] , and heroin [15,16] . MTEP, another antagonist of mGluR5, also can attenuate opiate selfadministration and opiate-seeking behavior in mice [17] . These data indicate mGluR5 plays a...

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“…We note that previous studies, although related, used approaches critically different from the relief-learning approach which is the focus of the present review (see also the discussions in Riebe et al 2012;Kong et al 2013): Seymour et al (2005) examined brain responses triggered by stimuli predicting a reduction of tonic pain, Leknes et al (2011) used a procedure involving the omission of a painful stimulus, and Kim et al (2006) as well as Levita et al (2012) studied brain responses during instrumental avoidance of an aversive outcome. Interestingly, reward centers of the brain, i.e., ventral striatum and orbitofrontal cortex, seem to be implicated in all these cases (see also the discussion of the role of these activations in active avoidance learning in Ilango et al 2012).…”

Section: Relief-learningmentioning

confidence: 99%

Pain-relief learning in flies, rats, and man: basic research and applied perspectives

et al. 2014

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Memories relating to a painful, negative event are adaptive and can be stored for a lifetime to support preemptive avoidance, escape, or attack behavior. However, under unfavorable circumstances such memories can become overwhelmingly powerful. They may trigger excessively negative psychological states and uncontrollable avoidance of locations, objects, or social interactions. It is therefore obvious that any process to counteract such effects will be of value. In this context, we stress from a basic-research perspective that painful, negative events are "Janus-faced" in the sense that there are actually two aspects about them that are worth remembering: What made them happen and what made them cease. We review published findings from fruit flies, rats, and man showing that both aspects, respectively related to the onset and the offset of the negative event, induce distinct and oppositely valenced memories: Stimuli experienced before an electric shock acquire negative valence as they signal upcoming punishment, whereas stimuli experienced after an electric shock acquire positive valence because of their association with the relieving cessation of pain. We discuss how memories for such punishment-and relief-learning are organized, how this organization fits into the threat-imminence model of defensive behavior, and what perspectives these considerations offer for applied psychology in the context of trauma, panic, and nonsuicidal self-injury.The acknowledged "negative" mnemonic effects of adverse experiences mostly relate to what happens before the onset of an aversive, painful event. However, there is a less widely acknowledged type of memory that relates to what happens after the offset of or after escape from such a painful event, at the moment of "relief" (Fig. 1) (we use "relief" to refer specifically to the acute effects of punishment offset; an equally legitimate yet broader use of the word in, e.g., "fear relief," encompasses any process that eases fear [Riebe et al. 2012]). Indeed, in experimental settings, it turns out that stimuli experienced before and during a punishing episode are later avoided as they signal upcoming punishment, whereas stimuli experienced after a painful episode can subsequently prompt approach behavior, arguably (Box 1) because of their association with the relieving cessation of pain (Konorski 1948;Smith and Buchanan 1954;Wolpe and Lazarus 1966;Zanna et al. 1970;Solomon and Corbit 1974;Schull 1979;Solomon 1980;Wagner 1981;Walasek et al. 1995;Tanimoto et al. 2004;Yarali et al. 2008Yarali et al. , 2009bAndreatta et al. 2010Andreatta et al. , 2012Yarali and Gerber 2010;Ilango et al. 2012;Navratilova et al. 2012;Diegelmann et al. 2013b); for a corresponding finding in the appetitive domain, see Hellstern et al. (1998) andFelsenberg et al. (2013). Such relief can both support the learning of the cues associated with the disappearance of the threat and reinforce those behaviors that helped to escape it. Obviously, the positive conditioned valence of and ensuing learned approach behavi...

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Avoidance of harm and anxiety: A role for the nucleus accumbens

Cited by 124 publications

References 95 publications

Neural basis of decision making guided by emotional outcomes

Neural basis of decision making guided by emotional outcomes

Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats

Pain-relief learning in flies, rats, and man: basic research and applied perspectives

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