Logical fallacies and misinterpretations that hinder progress in translational addiction neuroscience

Abstract

Substance use disorders (SUDs) are heterogeneous and complex, making the development of translationally predictive rodent and nonhuman 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 theoretical commentary, we first describe the development of animal models of substance use behaviors 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 to better bridge the translational divide between animal models, the clinical condition of SUDs, and current and future regulatory pathways for intervention development.

Ovarian Hormones Regulate Nicotine Consumption and Accumbens Glutamatergic Plasticity in Female Rats

“…However, neither duration of E2 treatment nor the addition of E2’s metabolite, E1, reversed the OVX-induced decreases in nicotine consumption. It is important to note that the brain and the environment interact bidirectionally, ultimately contributing to the emission of behaviors ( Strickland et al, 2022 ). As such, neurobiological mechanisms may be rapidly impacted by stimuli; however, behavior is complex and likely requires various other factors, including the presence of other hormones that regulate the female reproductive cycle (e.g., progesterone, luteinizing hormone, and follicle-stimulating hormone), restoration of the hypothalamic-pituitary-ovarian axis ( Mikhael et al, 2019 ) among others.…”

Hyperbolic discounting and exponentiated demand: Modeling demand for cigarettes in three dimensions

“…This "real cost" adjustment does not occur in the hyperbolic models. Whether there is some such thing as "essential value" that can be extracted from these models is a more detailed discussion than can occur here (see Strickland, Stoops, et al, 2022 for more discussion on this topic). Further research is required between models of demand to determine which equations produce the most meaningful parameter estimates relative to goodness-of-fit metrics.…”

Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats

“…The lack of medications for CUD is largely due to candidate medications failing in clinical trials despite promising preclinical results. The challenge of failed translation is not unique to CUD research [ 2 ]; however, we argue that in order to produce a more representative and translationally relevant body of knowledge on the neurobiological basis and potential treatments for addiction, studies need to use animal models validated to induce addiction-like features like those observed in women and men with CUD and consider biological sex as a variable [ 3 ].…”