Title : Dynamics of the anti-reward system
Abstract:
Much tragedy and stigmatization arise from what appears to the uninformed as a selfish, insatiable urge to consume substances for those with severe substance use disorder (SUD). Indeed, the lengths to which addicted persons often go to for substances can violate personal and societal values and create great personal risk. A robust neurobiological explanation exists for this which has not yet been elaborated fully in the literature: an antireward system centred within the lateral habenula (LHb), rostral medial tegmentum, ventral tegmental area and nucleus accumbens (NAc) is present in healthy people to amplify signals which indicate negative reward. Developed to help persons avoid repeats of negative experience, this system amplifies negative dopamine spikes previously encoded through reward prediction error determined by the NAc. In short, previous negative experiences, when cued externally or internally, result in an amplification of the negative dopamine state previously experienced. Through engaging the rest of the limbic system and hypothalamus, a strong dysphoria is experienced signalling avoidance of the experience.
Through the progression of addiction, this system is hijacked to compulsively push persons to continue substance use to avoid activation of tremendous dysphoria and craving (withdrawal). Over time, Pavlovian learning results in a positive dopamine burst in the mesolimbic pathway when cues to substances are experienced. As tolerance and dependence develop, a negative dopamine spike likewise occurs when anticipated (cued) reward is omitted. This in turn, activates the LHb. Reward omissions activate neurons in the lateral habenula (LHb), which indirectly inhibits DA neurons via activation of GABAergic neurons in the rostromedial tegmental nucleus (RMTg). Repeated activation of the LHb results in neuroadaptations producing hyperexcitability and hyperreactivity, further increasing amplification of negative dopamine states. This is experienced as learning to avoid negative dopamine states at all costs. Withdrawal has become learned and, through the anti-reward system, becomes the predominant driver for continued use. The greater the severity of SUD, the greater the neuroadaptations in the anti-reward system and dysphoria experienced with omission of substances.
