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    Review of 'Reward and adversity processing circuits, their competition and interactions with dopamine and serotonin signaling.'

    Reward and adversity processing circuits, their competition and interactions with dopamine and serotonin signaling.Crossref
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    Reward and adversity processing circuits, their competition and interactions with dopamine and serotonin signaling.

    We propose that dorsal anterior cingulate cortex (dACC), anterior insula (AI) and adjacent caudolateral orbitofrontal cortex (clOFC), project to lateral habenula (LHb) and D2 loop of ventral striatum (VS), forming a functional adversity processing circuit, directed towards inhibitory avoidance and self-control. This circuit learns what is bad or harmful to us, evaluates and predicts risks - to stop us from selecting and going/moving for the bad or suboptimal choices that decrease our well-being and survival chances. Proposed role of dACC is to generate a WARNING signal when things are going (or might end) bad or wrong to prevent negative consequences: pain, harm, loss or failure. The AI signals about bad, low, noxious and aversive qualities, which might make us sick or cause discomfort. These cortical adversity processing regions activate directly and indirectly (via D2 loop of VS) the LHb, which then inhibits dopamine and serotonin release (and is reciprocally inhibited by VTA/SNc, DRN) to avoid choosing and doing things leading to harm or loss, but also to make us feel worse, even down when overstimulated. We propose that dopamine attenuates output of the adversity processing circuit, thus decreasing inhibitory avoidance and self-control, while serotonin attenuates dACC, AI, clOFC, D1 loop of VS, LHb, amygdala and pain pathway. Thus, by reciprocal inhibition, by causing dopamine and serotonin suppression - and by being suppressed by them, the adversity processing circuit competes with reward processing circuit for control of choice behaviour and affective states. We propose stimulating effect of dopamine and calming inhibitory effect of serotonin on the active avoidance circuit involving amygdala, linked to threat processing, anger, fear, self-defense and violence. We describe causes and roles of dopamine and serotonin signaling in health and in mental dysfunctions. We add new idea on ventral ACC role in signaling that we are doing well and inducing serotonin, when we gain/reach safety, comfort, valuable resources (social or biological rewards), affection and achieve goals.

      Review information

      This work has been published open access under Creative Commons Attribution License CC BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com.

      ventral striatum, affective cortico-striato-thalamo-cortical loop,active avoidance, amygdala, violence, self-defence,depression, anxiety, schizophrenia, mood disorders, addiction, motivation, impulsivity,dACC, vACC, anterior insula, medial OFC, lateral habenula, VTA, DRN,inhibitory avoidance, inhibitory self-control,adversity processing circuit,reward processing circuit,serotonin signaling,dopamine signaling,decision makig , value-based learning, goal-directed control of behaviour, well-being

      Review text

      1. During the complete review process, it has been reflected that sufficient references are not given on all those statements based on which, authors are proposing their hypothesis.

      2.Authors are claiming or proposing many statements e.g. on page 2 under the title “Dorsal Anterior Cingulate Cortex” and likewise on other topics, but it has been reflected that the poor scientific citation or elaborations of results are given.

      3. Regarding the DA signaling, authors have described the D1 loop and D2 loop but it has been suggested to include the evidences from the heterogeneity of D1-D3 heteromer complex etc.

      4. Authors have described the effect of DA and serotonin signaling on APC or RPC. Since the ultimate effect of either DA or serotonin may precede several molecular mechanism e.g it has been now confirmed that activation/deactivation of secondary intracellular cascade, activation of several transcription factor and so as to induce gene expression may now be well claimed to become the final common pathway of any psychiatric disorders or mental condition. Hence it has been suggested to include the evidences of all these rate limiting steps so as to build strong hypothesis.


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