Reward and adversity processing circuits: their competition and interactions with dopamine and serotonin signaling

Abstract

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 (APC), directed toward inhibitory avoidance and self-control. This circuit learns what is bad or harmful to us and 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. The 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 directly and indirectly activate (via D2 loop of VS) the LHb, which then inhibits dopamine (DA) and serotonin release (and is reciprocally inhibited by ventrotegmental area/substantia nigra compacta [VTA/SNc], dorsal and median raphe nucleus [DRN, MRN]) to avoid choosing and doing things leading to harm or loss, and to make us feel worse or even down when overstimulated. We propose that DA attenuates the output of the APC, thus decreasing inhibitory avoidance and self-control, while serotonin attenuates the dACC, AI, clOFC, D1 loop of VS, LHb, the amygdala, and pain pathway. Thus, by reciprocal inhibition, by causing DA and serotonin suppression and by being suppressed by them, the APC competes with the reward-processing circuit (RPC) for control of choice behavior and affective states. We propose the stimulating effect of DA and the calming inhibitory effect of serotonin on the active avoidance circuit involving the amygdala, linked to threat processing, anger, fear, self-defense, and violence. We describe the causes and roles of DA and serotonin signaling in health and in mental dysfunctions. We add new ideas on the role of the ventral anterior cingulate cortex (vACC) in signaling that we are doing well and in inducing serotonin, when we gain/reach safety, comfort, valuable resources (social or biological rewards), affection, and achieve goals.