Reid D. Landes

Remember the future: working memory training decreases delay discounting among stimulant addicts

BACKGROUND Excessive discounting of future rewards has been observed in a variety of disorders and has been linked both to valuation of the past and to memory of past events. METHODS To explore the functionality of discounting and memory, we examined whether training of working memory would result in less discounting of future rewards. In this study, 27 adults in treatment for stimulant use were randomly assigned to receive either working memory training or control training according to a yoked experimental design. Measures of delay discounting and several other cognitive behaviors were assessed pre- and posttraining. RESULTS Rates of discounting of delayed rewards were significantly reduced among those who received memory training but were unchanged among those who received control training; other cognitive assessments were not affected by memory training. Discount rates were positively correlated with memory training performance measures. CONCLUSIONS To our knowledge, this is the first study demonstrating that neurocognitive training on working memory decreases delay discounting. These results offer further evidence of a functional relationship between delay discounting and working memory.

Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids

Glucocorticoids depress bone formation by inhibiting osteoblastogenesis and increasing osteoblast apoptosis. However, the role of bone resorption in the initial rapid phase of bone loss characteristic of glucocorticoid-induced osteoporosis is unexplained, and the reason for the efficacy of bisphosphonates in this condition remains unknown. We report that in murine osteoclast cultures, glucocorticoids prolonged the baseline survival of osteoclasts and antagonized bisphosphonate-induced caspase activation and apoptosis by a glucocorticoid receptor-mediated action. Consistent with the in vitro evidence, in a murine model of glucocorticoid-induced osteoporosis, the number of cancellous osteoclasts increased, even though osteoclast progenitor number was reduced. Moreover, in mice receiving both glucocorticoids and bisphosphonates, the expected proapoptotic effect of bisphosphonates on osteoclasts was abrogated, as evidenced by maintenance of osteoclast numbers and, additionally, loss of bone density. In contrast, bisphosphonate administration prevented glucocorticoid-induced osteoblast apoptosis. These results indicate that the early loss of bone with glucocorticoid excess is caused by extension of the life span of pre-existing osteoclasts, an effect not preventable by bisphosphonates. Therefore, the early beneficial effects of these agents must be due, in part, to prolonging the life span of osteoblasts.

Delay Discounting, Locus of Control, and Cognitive Impulsiveness Independently Predict Tobacco Dependence Treatment Outcomes in a Highly Dependent, Lower Socioeconomic Group of Smokers

Tobacco use disproportionately affects lower socioeconomic status (SES) groups. Current explanations as to why lower SES groups respond less robustly to tobacco control efforts and tobacco dependence treatment do not fully account for this disparity. The identification of factors that predict relapse in this population might help to clarify these differences. Good candidates for novel prognostic factors include the constellation of behaviors associated with executive function including self-control/impulsiveness, the propensity to delay reward, and consideration and planning of future events. This study examined the ability of several measures of executive function and other key clinical, psychological, and cognitive factors to predict abstinence for highly dependent lower SES participants enrolled in intensive cognitive-behavioral treatment for tobacco dependence. Consistent with predictions, increased discounting and impulsiveness, an external locus of control as well as greater levels of nicotine dependence, stress, and smoking for negative affect reduction predicted relapse. These findings suggest that these novel factors are clinically relevant in predicting treatment outcomes and suggest new targets for therapeutic assessment and treatment approaches.

Delay discounting predicts adolescent substance abuse treatment outcome

The purpose of the current study was to identify predictors of delay discounting among adolescents receiving treatment for marijuana abuse or dependence, and to test delay discounting as a predictor of treatment outcome. Participants for this study were 165 adolescents (88% male) between the ages of 12 and 18 (mean age = 15.8 years; standard deviation = 1.3 years) who enrolled in a clinical trial comparing three behavioral treatments for adolescent marijuana abuse or dependence. Participants completed a delay discounting task at treatment onset for

Single- and cross-commodity discounting among cocaine addicts: the commodity and its temporal location determine discounting rate

100 and

Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats

1,000 of hypothetical money and marijuana. Overall, smaller magnitude rewards were discounted more than larger magnitude rewards. Delay discounting rates were concurrently related to demographic variables (socioeconomic status, race). Delay discounting of

The effects of reduced cigarette smoking on discounting future rewards: An initial evaluation

1,000 of money predicted during treatment abstinence outcomes among adolescent marijuana abusers, over and above the effects of type of treatment received. Teens who show higher levels of discounting of the future may be an important subgroup to identify at treatment onset. Youth with a greater tendency to discount the future may require different intervention strategies that address their impulsivity (e.g., targeting executive function or inhibitory control) and/or different schedules of reinforcement to address their degree of preference for immediate rewards.

Hypothetical Intertemporal Choice and Real Economic Behavior: Delay Discounting Predicts Voucher Redemptions During Contingency-Management Procedures

RationaleIntertemporal choice has provided important insights into understanding addiction, predicted drug-dependence status, and outcomes of treatment interventions. However, such analyses have largely been based on the choice of a single commodity available either immediately or later (e.g., money now vs. money later). In real life, important choices for those with addiction depend on making decisions across commodities, such as between drug and non-drug reinforcers. To date, no published study has systematically evaluated intertemporal choice using all combinations of a drug and a non-drug commodity.ObjectivesIn this study, we examine the interaction between intertemporal choice and commodity type in the decision-making process of cocaine-dependent individuals.MethodsThis study of 47 treatment-seeking cocaine addicts analyzes intertemporal choices of two commodities (equated amounts of cocaine and money), specifically between cocaine now vs. cocaine later (C-C), money now vs. money later (M-M), cocaine now vs. money later (C-M), and money now vs. cocaine later (M-C).ResultsCocaine addicts discounted significantly more in the C-C condition than in M-M (P = 0.032), consistent with previous reports. Importantly, the two cross-commodity discounting conditions produced different results. Discounting in C-M was intermediate to the C-C and M-M rates, while the greatest degree of discounting occurred in M-C.ConclusionsThese data indicate that the menu of commodities offered alter discounting rates in intertemporal choice and that the greatest rate is obtained when the drug is the later available commodity. Implications for understanding intertemporal choices and addiction are addressed.

Temporal and Probability Discounting by Cigarette Smokers Following Acute Smoking Abstinence

Our studies examined pharmacokinetic mechanisms involved in high-affinity (K(d) approximately 11 nM) monoclonal antibody-based antagonism of (+)-methamphetamine-induced locomotor effects. Male rats received (+)-methamphetamine (0.3, 1, or 3 mg/kg i.v.) followed 30 min later by saline or anti-(+)-methamphetamine monoclonal antibody. All groups received a constant dose of monoclonal antibody that was equimolar in binding sites to the body burden of a 1 mg/kg i.v. (+)-methamphetamine dose 30 min after administration. The monoclonal antibody antagonized locomotor effects due to 0.3 and 1 mg/kg (+)-methamphetamine. In contrast, monoclonal antibody treatment increased locomotor activity due to 3 mg/kg (+)-methamphetamine. We also investigated the serum and brain pharmacokinetics of (+)-methamphetamine without and with the monoclonal antibody. Rats received (+)-methamphetamine (1 mg/kg i.v.) followed by saline or monoclonal antibody treatment at 30 min. The monoclonal antibody significantly increased serum methamphetamine concentrations and significantly decreased brain methamphetamine concentrations. These data indicate that anti-(+)-methamphetamine monoclonal antibody-induced pharmacodynamics are complex, but are related to time-dependent changes in (+)-methamphetamine brain distribution.

Delay of smoking gratification as a laboratory model of relapse: effects of incentives for not smoking, and relationship with measures of executive function.

To determine whether reduction of smoking via contingency management in depen-dent smokers would decrease the discounting of delayed reinforcers compared with smokers who did not reduce their smoking, moderate to heavy cigarette smokers were randomly assigned to one of two conditions: a contingency management condi-tion and a control condition. In three phases (baseline discounting determination for hypothetical money and cigarettes, implementation of a contingency management or control condition, and postintervention discounting determination), the procedure to reinforce reduction in cigarette smoking produced CO decreases in all subjects exposed to that procedure. Discounting decreased significantly for both cigarettes and money among the group for whom smoking reductions were reinforced, whereas the control group showed no significant change for either commodity. Reductions in smoking can lead to reductions in discounting, and increased discounting in current smokers may be a reversible effect of nicotine dependence.