Modelling Differential Vulnerability to Substance Use Disorder in Rodents: Neurobiological Mechanisms

Abstract

Despite the prevalence of drug use within society, only a subset of individuals actively taking addictive drugs lose control over their intake and develop compulsive drug-seeking and intake that typifies substance use disorder (SUD). Although research in this field continues to be an important and dynamic discipline, the specific neuroadaptations that drive compulsive behaviour in humans addicted to drugs and the neurobiological mechanisms that underlie an individual’s innate susceptibility to SUD remain surprisingly poorly understood. Nonetheless, it is clear from research within the clinical domain that some behavioural traits are recurrently co-expressed in individuals with SUD, thereby inviting the hypothesis that certain behavioural endophenotypes may be predictive, or at least act in some way, to modify an individual’s probability for developing this disorder. The analysis of such endophenotypes and their catalytic relationship to the expression of addiction-related behaviours has been greatly augmented by experimental approaches in rodents that attempt to capture diagnostically relevant aspects of this progressive brain disorder. This work has evolved from an early focus on aberrant drug reinforcement mechanisms to a now much richer account of the putatively impaired cognitive control processes that ultimately determine individual trajectories to compulsive drug-related behaviours. In this chapter we discuss the utility of experimental approaches in rodents designed to elucidate the neurobiological and genetic underpinnings of so-called risk traits and how these innate vulnerabilities collectively contribute to the pathogenesis of SUD.