Amanda J. Quisenberry

Therapeutic Opportunities for Self-Control Repair in Addiction and Related Disorders: Change and the Limits of Change in Trans-Disease Processes.

Contemporary neuroeconomic approaches hypothesize that self-control failure results from drugs annexing normal learning mechanisms that produce pathological reward processing and distort decision making as a result from the dysregulation of two valuation systems. An emphasis on processes shared across different diseases and disorders is at odds with the contemporary approach that assumes unique disease etiologies and treatments. Studying trans-disease processes can identify mechanisms that operate in multiple disease states and ascertain if factors that influence processes in one disease state may be applicable to all disease states. In this article we review the dual model of self-control failure, the Competing Neurobehavioral Decision System approach, the relationship of delay discounting to the relative control of these two systems, and evidence that the executive system can be strengthened. Future research that could result in more potent interventions for executive system improvement and potential constraints on the repair of self-control failure are discussed.

A Competing Neurobehavioral Decision Systems model of SES-related health and behavioral disparities

We propose that executive dysfunction is an important component relating to the socio-economic status gradient of select health behaviors. We review and find evidence supporting an SES gradient associated with (1) negative health behaviors (e.g., obesity, excessive use of alcohol, tobacco and other substances), and (2) executive dysfunction. Moreover, the evidence supports that stress and insufficient cognitive resources contribute to executive dysfunction and that executive dysfunction is evident among individuals who smoke cigarettes, are obese, abuse alcohol, and use illicit drugs. Collectively these data support the dual system model of cognitive control, referred to here as the Competing Neurobehavioral Decision Systems hypothesis. The implications of these relationships for intervention and social justice considerations are discussed.

The Experimental Tobacco Marketplace I: Substitutability as a Function of the Price of Conventional Cigarettes

INTRODUCTION Behavioral economic studies of nicotine product consumption have traditionally examined substitution between two products and rarely examined substitution with more products. Increasing numbers of tobacco products available for commercial sale leads to more possible cross-product interactions, indicating a need to examine substitution in more complex arrangements that closely mirror the tobacco marketplace. METHODS The experimental tobacco marketplace (ETM) is an experimental online store that displays pictures, information, and prices for several tobacco products. Smokers were endowed with an account balance based on their weekly tobacco purchases. Participants then made potentially real purchases for seven (Experiment 1) or six (Experiment 2) tobacco/nicotine products under four price conditions for conventional cigarettes while prices for other products remained constant. Smokers returned 1 week later to report tobacco/nicotine use and return unused products for a refund. RESULTS In Experiment 1 (n = 22), cigarette purchasing decreased as a function of price. Substitution was greatest for electronic cigarettes and cigarillos and significant for electronic cigarettes. Experiment 2 (n = 34) was a replication of Experiment 1, but with cigarillos unavailable in the ETM. In Experiment 2, cigarette purchases decreased as a function of price. Substitution was robust and significant for electronic cigarettes and Camel Snus. CONCLUSIONS The ETM is a novel, practical assay that mimics the real-world marketplace, and functions as a simple research tool for both researchers and participants. Across the two experiments the product mix in the ETM altered which products functioned as substitutes suggesting complex interactions between purchasing and product availability. IMPLICATIONS This article adds a novel method of collecting purchasing data that mimics real world purchasing to the existing literature. The ETM is a practical avenue by which to study both hypothetical and potentially real purchasing.

Competing neurobehavioral decision systems theory of cocaine addiction: From mechanisms to therapeutic opportunities.

Cocaine dependence is a difficult-to-treat, chronically relapsing disorder. Multiple scientific disciplines provide distinct perspectives on this disorder; however, connections between disciplines are rare. The competing neurobehavioral decision systems (CNDS) theory posits that choice results from the interaction between two decision systems (impulsive and executive) and that regulatory imbalance between systems can induce pathology, including addiction. Using this view, we integrate a diverse set of observations on cocaine dependence, including bias for immediacy, neural activity and structure, developmental time course, behavioral comorbidities, and the relationship between cocaine dependence and socioeconomic status. From the CNDS perspective, we discuss established and emerging behavioral, pharmacological, and neurological treatments and identify possible targets for future treatments. The ability of the CNDS theory to integrate diverse findings highlights its utility for understanding cocaine dependence and supports that dysregulation between the decision systems contributes to addiction.

Modafinil alone and in combination with low dose amphetamine does not establish conditioned place preference in male Sprague-Dawley rats

Modafinil is a novel wake-promoting drug with FDA approval for the treatment of narcolepsy, shift work sleep disorder, and sleep apnea. It is also prescribed for many off-label uses such as ADHD and it is currently being assessed as a treatment for psychostimulant dependence. Previous research assessing the abuse liability of modafinil in animals and humans suggests it is less potent and has a low abuse potential compared to traditional psychomotor stimulants. However, modafinil has not been carefully assessed in combination with other psychostimulant drugs. The current study used an unbiased place conditioning procedure simultaneously with locomotor screening procedures to assess the combined behavioral effects of modafinil and d-amphetamine in adult male Sprague-Dawley rats. Eight 30-min conditioning trials were conducted in a 2 compartment apparatus with distinct visual and tactile cues. Drug and vehicle conditioning trials were alternated with 1 trial per day separated by 24 hr. On drug conditioning trials, rats were administered either modafinil (64 mg/kg, i.g.), d-amphetamine (0.3 or 2.0 mg/kg, s.c.), a combination of modafinil (64 mg/kg) and d-amphetamine (0.3 mg/kg), or vehicle injections. On vehicle conditioning trials, all groups received vehicle injections. Preference for either compartment was assessed by recording time spent in each compartment during a 15-min test conducted 24 hr after the last conditioning trial. Results indicated that this low oral dose of modafinil did not significantly increase locomotor activity or establish conditioned place preference (CPP). Moreover, modafinil did not significantly alter the hyperlocomotor or CPP effects of d-amphetamine. To confirm that modafinil is behaviorally active at this low oral dose, a separate assessment of horizontal and vertical activity was conducted with male Sprague-Dawley rats in an open field apparatus. Results confirmed that modafinil increased locomotor activity relative to vehicle, with increases in vertical activity especially prominent, a measure that was not assessed in place conditioning trials. Although the current results predict a low abuse liability with concurrent use of modafinil and d-amphetamine, additional research with higher dose combinations may be warranted before ruling out the possibility that these drugs could have additive or synergistic effects.

Order in the absence of an effect: Identifying rate-dependent relationships.

The heterogeneity of group data can obscure a significant effect of an intervention due to differential baseline scores. Instead of discarding the seemingly heterogeneous response set, an orderly lawful relationship could be present. Rate dependence describes a pattern between a baseline and the change in that baseline following some intervention. To highlight the importance of analyzing data from a rate-dependent perspective, we (1) briefly review research illustrating that rate-dependent effects can be observed in response to both drug and non-drug interventions in varied schedules of reinforcement in clinical and preclinical populations; (2) observe that the process of rate-dependence likely requires multiple parts of a system operating simultaneously to evoke differential responding as a function of baseline; and (3) describe several statistical methods for consideration and posit that Oldhams correlation is the most appropriate for rate-dependent analyses. Finally, we propose future applications for these analyses in which the level of baseline behavior exhibited prior to an intervention may determine the magnitude and direction of behavior change and can lead to the identification of subpopulations that would be benefitted. In sum, rate dependence is an invaluable perspective to examine data following any intervention in order to identify previously overlooked results.

Toward Narrative Theory: Interventions for Reinforcer Pathology in Health Behavior

Reinforcer pathology describes the interaction between excessive devaluation of delayed rewards and excessive valuation of commodities such as drugs or food. In isolation, both components of reinforcer pathology increase risk for substance-use disorders and other maladaptive health behaviors (e.g., poor diet); in combination, these components synergistically increase risk. In this chapter, we review evidence that reinforcer pathology may arise from imbalance between two competing neurobehavioral decision systems (CNDS)—the impulsive system, comprising the limbic and paralimbic brain regions, and the executive system, comprising the prefrontal and parietal cortices. To correct imbalance between these systems and restore normative decision making, we introduce narrative theory, a novel intervention framework that seeks to harness humans’ unique sensitivity to language and storytelling in order to both understand and potentially treat the maladaptive decision making observed in addiction and other maladaptive health behaviors. We provide both an overview of methods used in investigations of narrative theory and a summary of effects of these methods on both discounting of delayed rewards and valuation of commodities that may damage health, such as drugs and energy-dense food.

Regret Expression and Social Learning Increases Delay to Sexual Gratification.

Objective Modification and prevention of risky sexual behavior is important to individuals’ health and public health policy. This study employed a novel sexual discounting task to elucidate the effects of social learning and regret expression on delay to sexual gratification in a behavioral task. Methods Amazon Mechanical Turk Workers were assigned to hear one of three scenarios about a friend who engages in similar sexual behavior. The scenarios included a positive health consequence, a negative health consequence or a negative health consequence with the expression of regret. After reading one scenario, participants were asked to select from 60 images, those with whom they would have casual sex. Of the selected images, participants chose one image each for the person they most and least want to have sex with and person most and least likely to have a sexually transmitted infection. They then answered questions about engaging in unprotected sex now or waiting some delay for condom-protected sex in each partner condition. Results Results indicate that the negative health outcome scenario with regret expression resulted in delayed sexual gratification in the most attractive and least STI partner conditions, whereas in the least attractive and most STI partner conditions the negative health outcome with and without regret resulted in delayed sexual gratification. Conclusions Results suggest that the sexual discounting task is a relevant laboratory measure and the framing of information to include regret expression may be relevant for prevention of risky sexual behavior.

Combined effects of modafinil and d-amphetamine in male Sprague-Dawley rats trained to discriminate d-amphetamine.

Modafinil is a novel wake-promoting drug with FDA approval for the treatment of sleep-related disorders that has recently been investigated as a potential agonist replacement therapy for psychostimulant dependence. Previous research in animals and humans indicates modafinil has a lower abuse liability than traditional psychostimulants, although few studies have carefully assessed modafinils stimulus properties in combination with other psychostimulants. The current study trained male Sprague-Dawley rats to discriminate subcutaneous injections of 0.3 mg/kg (n=8) or 1.0 mg/kg d-amphetamine (n=8) from saline under an FR 20 schedule of food reinforcement and substitution tests were administered with d-amphetamine (0.03-1.0 mg/kg, s.c.), modafinil (32-256 mg/kg, i.g.), and a low modafinil dose (32 mg/kg, i.g.) in combination with d-amphetamine (0.03-1.0 mg/kg, s.c.) to determine if these drugs have additive effects. The selective D2 dopamine agonist, PNU-91356A, was also tested as a positive control and ethanol and morphine were tested as negative controls. Results indicate that modafinil produced dose-dependent and statistically significant d-amphetamine-lever responding in both groups and nearly complete substitution in animals trained to discriminate 1.0 mg/kg d-amphetamine. Modafinil pretreatment slightly increased the discrimination of low d-amphetamine doses in animals trained to discriminate 0.3 mg/kg d-amphetamine. These results support previous findings that modafinil and d-amphetamine may have additive effects. In consideration of recent interests in modafinil as an agonist treatment for psychostimulant dependence, additional preclinical investigations utilizing other methodologies to examine modafinil in combination with other stimulants, such as behavioral sensitization paradigms or drug self-administration, may be of interest.

Reinforcer Pathology: The Behavioral Economics of Abuse Liability Testing

Understanding the abuse liability of novel drugs is critical to understanding the risk these new compounds pose to society. Behavioral economics, the integration of psychology and economics, can be used to predict abuse liability of novel substances. Here, we describe the behavioral economic concept of reinforcer pathology and how it may predict the use of novel drugs in existing drug‐users and initiation of use in the drug‐naive.