Understanding Addiction Using Animal Models

Abstract

Drug addiction is a neuropsychiatric disorder with grave personal consequences that has an extraordinary global economic impact. Despite decades of research, the options available to treat addiction are often ineffective because our rudimentary understanding of drug-induced pathology in brain circuits and synaptic physiology inhibits the rational design of successful therapies. This understanding will arise first from animal models of addiction where experimentation at the level of circuits and molecular biology is possible. We will review the most common preclinical models of addictive behavior and discuss the advantages and disadvantages of each. This includes non-contingent models in which animals are passively exposed to rewarding substances, as well as widely used contingent models such as drug self-administration and relapse. For the latter, we elaborate on the different ways of mimicking craving and relapse, which include using acute stress, drug administration or exposure to cues and contexts previously paired with drug self-administration. We further describe paradigms where drug-taking is challenged by alternative rewards, such as appetitive foods or social interaction. In an attempt to better model the individual vulnerability to drug abuse that characterizes human addiction, the field has also established preclinical paradigms in which drug-induced behaviors are ranked by various criteria of drug use in the presence of negative consequences. Separation of more vulnerable animals according to these criteria, along with other innate predispositions including goal- or sign-tracking, sensation-seeking behavior or impulsivity, has established individual genetic susceptibilities to developing drug addiction and relapse vulnerability. We further examine current models of behavioral addictions such as gambling, a disorder included in the DSM-5, and exercise, mentioned in the DSM-5 but not included yet due to insufficient peer-reviewed evidence. Finally, after reviewing the face validity of the aforementioned models, we consider the most common standardized tests used by pharmaceutical companies to assess the addictive potential of a drug during clinical trials.

One Is Not Enough: Understanding and Modeling Polysubstance Use

“…Behavioral models of drug addiction are used to examine the neurobiological underpinnings of the development, maintenance and relapse to drug use. The most commonly used models are locomotor sensitization (a progressive and persistent increase in locomotor responses to the same dose of a drug), conditioned place preference (CPP; a test of drug reward measured as an increase in time spent in a drug-paired chamber) and drug self-administration (response-contingent intake of drug) (see Spanagel, 2017;Kuhn et al, 2019 for review). Experimental designs using these models vary across a number of pharmacological and non-pharmacological parameters including contingency of drug use, amount of access to drug, context associated with drug use, and routes of administration.…”

New Developments in Behavioral Pharmacology

“…In this study, it was identified that at 3-week post-ovariectomy appears anxietylike behavior, but from 6-week post-ovariectomy in addition to anxiety-like behavior, also increases depression-like behavior in rats, supporting an experimental model of surgical post-menopause [25] measured by scoring ambulation, rearing or nose approaching to an object; sexual behavior can be measured by conditioned place preference, number of mounts, latency and number of ejaculations. All these behaviors are normally studied under controlled environments that are designed specifically to the required behavioral display and every feature of the environment; the experimental subjects or chemical agents with probed effects on humans have been studied in this environment with the purpose of establishing these manipulations as models of a specific behavior (see Table 2) as spatial learning and memory, or models of specific pathologies behaviorally expressed as is the case of anxiety [28], depression [29], obsessive compulsive disorder [30], Parkinson [31], epilepsy [32] or addictive behaviors [33], and sleep deprivation [34], among others.…”

“…This review discusses the influence of hormones on brain function and behavior, and integrate information to explain how the brain and the body communicate reciprocally via hormones and other mediators, and in ways that influence brain and body health but which can also accelerate diseases processes when the mediators of allostasis are dysregulated [40] Addiction A review of the most popular behavioral models for the study of addictions such as conditioned place preference and self-administration and new models to study behavioral addictions as gambling and exercise addiction [33] Sleep disorders This review describes the Pitolisant (Wakix®), first-in-class antagonist/inverse agonist of the H3 receptor for the treatment of narcolepsy with or without cataplexy [41] face validity); and simulations as those uses of animal behavior that can inform on the etiology, pathophysiology, and treatment of human (mental) disorders (i.e., possess high construct validity). Further developments of this framework [45] advance the theory of validity, therefore improving the capability of researchers to evaluate animal models.…”

Introductory Chapter: Behavioral Pharmacology - From Basic to Clinical Research

“…Behavioral pharmacology is a multidisciplinary field of science focused on exploring and understanding the effects of chemical substances, hormones, and drugs on the behavior of humans and experimental animals, all with the final objective of understanding the neurobiological substrate of behavior and contributing in the development of therapeutic agents or pharmacologic tools for research in neurosciences [1]. The relative new popularity and accelerated growth of neurosciences have simultaneously led to an exponential growth on the scientific literature on this area that has been produced every day [2][3][4][5][6]. That makes necessary new strategies to be ready in a field that has been constantly actualized; for example, years ago, students with different backgrounds, who are graduates of psychology, medicine, or chemistry, had to study postgraduate trainings to specialize in the field of neurosciences.…”