Aggression Addiction and Relapse: A New Frontier in Psychiatry

There is an increased risk for abnormal or pathological aggression in individuals suffering from psychiatric disorders. Aggression is commonly ethologically demarcated as either appetitive or reactive, each with its own behavioral characteristics, functionality, and neural basis that may transition from adaptive to maladaptive depending on genetic and environmental factors. One type, pathological appetitive aggression, is hypothesized to result from excessive activation of evolutionary conserved reward circuits, which also mediate the rewarding effects of addictive drugs. Indeed, inappropriate appetitive aggression shows core features of addiction: aggression is often sought despite immediate or long-term adverse consequences, and relapse (recidivism) rates among violent offenders are as high as relapse rates in drug addiction. Despite these similarities, pathological aggression seeking has not been commonly incorporated into the conceptual framework of addiction and psychiatric disorders. Such a reconceptualization may positively impact therapeutic strategies to prevent pathological aggression and decrease recidivism (relapse) rates after incarceration or inpatient treatment.

Seminal studies from the Miczek laboratory established that aggressive mice will perform operant tasks to attack subordinate intruders (Fish et al, 2002), in a manner akin to rodents self-administering addictive drugs. In addition, we recently adapted the conditioned place preference (CPP) procedure, commonly used to study the rewarding effects of drugs, to study aggression reward. We showed that innately aggressive male CD-1 mice form a preference to an aggression-paired context (Golden et al, 2016), and as with addictive drugs, this preference persists over time (Golden et al, 2017a). However, self-administration and CPP are also readily observed with non-drug rewards like food and water, and therefore, are not sufficient metrics to conclude that a rewarding stimulus is being sought maladaptively or compulsively. In models of compulsive drug addiction, those criteria have been operationalized as drug self-administration, despite adverse consequences, high motivation to seek the drug, and relapse to drug seeking during abstinence (Deroche-Gamonet et al, 2004). On the basis of this consideration, we used established animal models of drug addiction and relapse to characterize motivated aggression in a population of CD-1 male mice (Golden et al, 2017b).

We reported several findings: (1) ~70% of aggressive mice learned to lever-press for aggressive interactions, (2) using models of relapse after forced abstinence, punishment-induced abstinence, or choice-based voluntary abstinence (Venniro et al, 2016), we showed that relapse to aggression seeking persists long after the last aggressive act, and (3) cluster analysis of the aggression-related measures identified a subset of mice that met criteria previously developed to denote compulsive addiction in rodent models (Deroche-Gamonet et al, 2004). Specifically, the cluster analysis identified a subset of ‘addicted’ mice (~19%) that exhibited intense operant-reinforced attack behavior, decreased likelihood to select an alternative palatable food reward over aggression, heightened relapse vulnerability and progressive ratio responding, and resilience to punishment-induced suppression of aggression-reinforced operant responding. Our studies suggest that preclinical addiction models can be used to identify the neural mechanisms controlling appetitive aggression and relapse, as well as pathological or compulsive manifestations of aggression (for an in-depth discussion of both the limitations and extensions of our studies, see Golden et al (2017a,b)).

In conclusion, we propose that appetitive aggression can be viewed within the context of compulsive behaviors, and that neurobiological and behavioral tools used to study compulsive drug seeking and relapse should be used to study brain mechanisms of this type of aggression, both preclinically and clinically. Finally, an appetitively motivated compulsion toward aggression might be an important endophenotype to include in dimensional formulations of psychopathology such as the National Institute of Mental Health’s Research Domain Criteria (RDoC), where aggression is currently mentioned only within the domain called negative-valence systems. We suggest that these conceptualizations of aggression are fundamentally incomplete and that some forms of aggression may be best understood as strong appetitive rewards, carrying the attendant risks of compulsive behavior.

Funding and disclosure

The authors declare no conflict of interest.