Logical Fallacies and Misinterpretations that Hinder Progress in Translational Addiction Neuroscience

Abstract

Substance use disorders (SUDs) are heterogenous and complex, making the development of translationally predictive rodent and non-human primate models to uncover their neurobehavioral underpinnings difficult. Neuroscience-focused outcomes have become highly prevalent, and with this, the notion that SUDs are disorders of the brain embraced as a dominant theoretical orientation to understand SUD etiology and treatment. These efforts, however, have led to few efficacious pharmacotherapies, and in some cases (as with cocaine or methamphetamine), no pharmacotherapies have translated from preclinical models for clinical use. In this review and theoretical commentary, we first describe the development of animal models of SUDs from a historical perspective. We then define and discuss three logical fallacies including 1) circular explanation, 2) affirming the consequent, and 3) reification that can apply to developed models. We then provide three case examples in which conceptual or logical issues exist in common methods (i.e., behavioral economic demand, escalation, and reinstatement). Alternative strategies to refocus behavioral models are suggested for the field in an attempt to better bridge the translational divide between animal models and the clinical condition of SUDs.

A general model of demand and discounting.

“…The direct relationship between time sensitivity of demand and the discount rate was linear and consistent across values of substitutability of the alternatives. Time sensitivity of demand (α) may reflect a characteristic of a commodity in context (Hursh & Silberberg, 2008), the behavioral history of an individual (Strickland et al, 2022), or a trait-like characteristic that applies across commodities for an individual (Odum, 2011). Regardless of the reason for differences in time sensitivity, it is important for it to be considered in the context of delay discounting.…”

“…This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. , the behavioral history of an individual (Strickland et al, 2022), or a trait-like characteristic that applies across commodities for an individual (Odum, 2011). Regardless of the reason for differences in time sensitivity, it is important for it to be considered in the context of delay discounting.…”

Socially Integrated Polysubstance (SIP) system: an open-source solution for continuous monitoring of polysubstance fluid intake in group housed mice

“…Substance use and addiction research has evolved significantly over the years, and it is now generally accepted that substance use disorders (SUDs) are disorders involving the brain that have complex biopsychosocial etiology (Strickland et al, 2022; Stull et al, 2022; Venniro et al, 2020). Despite impressive results from preclinical neuroscience research using rodent models, few new effective treatments have been successfully translated to the clinic.…”

“…Despite impressive results from preclinical neuroscience research using rodent models, few new effective treatments have been successfully translated to the clinic. This has led to questioning whether animal models are a valid method to study SUDs, and increasing emphasis placed on improving ethological relevance and connection to lived experience of people who use drugs (Ahmed et al, 2013; Field & Kersbergen, 2020; Negus & Banks, 2020; Strickland et al, 2022; Stull et al, 2022; Vandaele & Daeppen, 2022; Venniro et al, 2020). Specifically, features of the human condition that can be, but are not often, addressed using rodent models are: 1) voluntary timing and frequency of substance intake, 2) social environment during substance use, and 3) access to multiple substances and multiple concentrations of the same substance (including food and water as alternative reinforcers).…”

“…The human population displays a wide variety of individual differences in response to rewarding substances and a majority of people who use drugs do not go on to develop “problematic” use or diagnosis of SUD (Strickland et al, 2022; Stull et al, 2022; Vandaele & Daeppen, 2022; Venniro et al, 2020). The 2020 National Survey on Drug Use and Health reported SUD rates in respondents aged 12 and older between 1.0% (any opioid) and 10.2% (alcohol) (SAMHSA, 2020).…”