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OBJECTIVES: Massachusetts was among the first states to allow standing orders to facilitate pharmacy-based naloxone purchase and reduce opioid overdose deaths. We conducted a unique purchase trial to establish a valid measure of standing order naloxone in Massachusetts, using purchasers from two high priority populations to determine whether naloxone is less accessible to those who use illicit opioids than other potential purchasers. METHODS: A random sample of 200 retail pharmacies was selected from a statewide list. Each pharmacy underwent two purchase attempts - one by a person who used illicit opioids (PWUIO) and one by a potential bystander who did not use illicit opioids but had a relationship with someone at risk of opioid overdose. Purchases were conducted in accordance with a detailed purchase protocol between May 2018 and April 2019. Matched pairs analysis was used to identify statistically significant differences in purchase outcomes and experiences by purchaser type. RESULTS: Overall, 322 of 397 purchase attempts (81%) were successful, with no significant difference between PWUIO and bystanders (p=.221). Most purchases (93%) resulted in acquisition of single-step nasal naloxone (NARCAN; median cost $133.38). Forty percent of purchases included state-mandated verbal counseling, and PWUIO were significantly less likely to receive counseling than bystanders (30% vs. 51%, p$150 (25%), and requiring a prescription (15%). Chain pharmacies were significantly more likely to sell naloxone than independent pharmacies (86% vs. 53%, p

Traumatic brain injury (TBI) affects 2.8 million people annually in the United States, with significant populations suffering from ongoing cognitive dysfunction. Impairments in decision-making can have major implications for patients and their caregivers, often enduring for years to decades, yet are rarely explored in experimental TBI. In the current study, the Rodent Gambling Task (RGT), an Iowa Gambling Task analog, was used to assess risk-based decision-making and motor impulsivity after TBI. During testing, rats chose between options associated with different probabilities of reinforcement (sucrose) or punishment (timeout). To determine effects of TBI on learned behaviors versus the learning process, rats were trained either before, or after, a bilateral frontal controlled cortical impact TBI, and then assessed for 12 weeks. To evaluate the degree to which monoamine systems, such as dopamine, were affected by TBI, rats were given an amphetamine challenge, and behavior recorded. Injury immediately and chronically decreased optimal decision-making, and biased rats towards both riskier, and safer (but suboptimal) choices, regardless of prior learning history. TBI also increased motor impulsivity across time, reflecting ongoing neural changes. Despite these similarities in trained and acquisition rats, those that learned the task after injury demonstrated reduced effects of amphetamine on optimal decision-making, suggesting a lesser role of monoamines in post-injury learning. Amphetamine also dose-dependently reduced motor impulsivity in injured rats. This study opens up the investigation of psychiatric-like dysfunction in animal models of TBI and tasks such as the RGT will be useful in identifying therapeutics for the chronic post-injury period.

Purpose The purpose of the current study was to evaluate associations between geographic rurality and tobacco use patterns among adolescents. Methods High school students (N = 566) from north-central Appalachia reported on their lifetime and/or current use of cigarettes, electronic cigarettes (ECIGs), cigars, and smokeless tobacco. Geographic rurality was measured via the Isolation scale, whereby residential ZIP Codes determined the degree to which respondents have access to health-related resources. Latent class analysis (LCA) was used to identify discrete classes of adolescent tobacco users based on their use of tobacco products. Then, associations between participants' geographic rurality and class membership were evaluated using a series of multinomial logistic regressions. Findings LCA classified participants as Nonusers, Current ECIG Users, Cigarette/ECIG Experimenters, and Polytobacco Users. Individuals with higher Isolation scores were more likely to be Polytobacco Users and Cigarette/ECIG Experimenters than Nonusers, and were more likely to be Polytobacco Users than Current ECIG Users. Conclusions The continuous Isolation scale used in the present study predicted polytobacco use patterns among adolescents in a manner that is consistent with, while simultaneously expanding upon, prior work. Tobacco control practices and policies should be viewed through a lens that considers the unique needs of geographically isolated areas.

Traumatic brain injury (TBI) affects millions of individuals every year. Many of these injuries lead to lasting effects, particularly impairments in domains broadly classified as executive functions, such as impulse control and decision-making. While these impairments have been historically associated with frontal brain damage, other injuries such as concussion or parietal injury also contribute to similar dysfunction. However, it is unknown whether animal models of TBI would replicate these broad effects that are observed in human patients. In the current study, we delivered a unilateral parietal controlled cortical impact injury and assessed the performance of rats on a motoric task (rotarod) and a test of decision-making and impulsivity (rodent gambling task). TBI rats demonstrated significant motor impairments on the rotarod task; however, this did not extend to difficulties inhibiting motor actions (impulsivity). In addition, TBI caused chronic alterations to risk-based decision-making, extending out to 12 weeks post-injury. Specifically, rats with TBI preferred the riskiest, and most suboptimal option over all others. The current data suggest that models of unilateral TBI are sufficient for replicating some aspects of executive dysfunction (risky decision-making), while others are limited to frontal damage (impulsivity). These models may be used to develop therapeutics targeted at the chronic post-injury period when these symptoms often manifest in patients, a critically understudied area in preclinical TBI research.

Individuals with attention-deficit/hyperactivity disorder tend to make risker choices during probabilistic-discounting procedures. Thus, how common attention-deficit/hyperactivity disorder medications affect probabilistic discounting is of interest. In general, d-amphetamine increases risk-taking while atomoxetine has produced mixed effects in rats. Results from previous studies may result from genetic factors. Lewis and F344 rats have neurochemical differences that may be relevant to probabilistic discounting and how drugs affect such behavior. In this study, we evaluated dose-dependent effects of d-amphetamine and atomoxetine on probabilistic discounting of Lewis and F344. Male Lewis and F344 chose between one food pellet delivered 100% of the time and three food pellets delivered following decreasing probabilities of delivery (i.e. 100%, 66.7%, 33.3%, 16.5%, and 8.25%). Saline, d-amphetamine (0.1-1.8 mg/kg), and atomoxetine (0.1-7.8 mg/kg) were tested acutely. Lewis and F344 did not differ in choice at baseline. d-Amphetamine increased risky choice for both rat strains at low-to-moderate doses, although it did so at a lower dose (0.1 and 0.3 mg/kg) for F344 as compared to Lewis (0.3 mg/kg only). At high doses (1.0 and 1.8 mg/kg), d-amphetamine disrupted choice, increased frequencies of omitted trials, and reduced reinforcer sensitivity. Although atomoxetine increased frequencies of omitted trials at high doses (5.6 and 7.8 mg/kg), it had no effect on probabilistic discounting for either rat strain. Although Lewis and F344 differ in various types of impulsivity (i.e. motor, choice), with Lewis being the more impulsive of the two, the present results suggest that Lewis and F344 do not differ in risk-based decision-making. Effects of d-amphetamine on probabilistic discounting may be biology-dependent and differ from effects of atomoxetine.

Impulsive choice underlies several psychological disorders and can be assessed in laboratory rats using delay-discounting tasks, in which choice is for either one food pellet immediately or three food pellets after a delay. Choice for the smaller, immediate reinforcer is considered the impulsive choice. Lewis (LEW) and Fischer 344 (F344) rats differ in the number of impulsive choices made during this task when singly housed, with LEW choosing the impulsive option more often. Due to increasing recommendations to provide environmental enrichment as a component of animal-husbandry practices, a systematic replication of two previous studies was conducted using pair-housed LEW and F344. Delay discounting was assessed with pair-housed LEW and F344 and compared to previous data from singly housed LEW and F344 collected from the same laboratory. Results showed that differences in impulsive choice between the two strains were attenuated with pair housing. The main result driving this change appears to be an increase in impulsive choice in pair-housed F344 relative to singly housed F344.

Stroke is a world-wide leading cause of death and long-term disability with concurrent secondary consequences that are largely comprised of mood dysfunction, as well as sensory, motor, and cognitive deficits. This review focuses on the cognitive deficits associated with stroke specific to executive dysfunction (including decision making, working memory, and cognitive flexibility) in humans, non-human primates, and additional animal models. Further, we review some of the cellular and molecular underpinnings of the individual components of executive dysfunction and their neuroanatomical substrates after stroke, with an emphasis on the changes that occur during biogenic monoamine neurotransmission. We concentrate primarily on changes in the catecholaminergic (dopaminergic and noradrenergic) and serotonergic systems at the levels of neurotransmitter synthesis, distribution, re-uptake, and degradation. We also discuss potential secondary stroke-related behavioral deficits (specifically, post-stroke depression as well as drug-abuse potential and addiction) and their relationship with stroke-induced deficits in executive function, an especially important consideration given that the average age of the human stroke population is decreasing. In the final sections, we address pharmacological considerations for the treatment of ischemia and the subsequent functional impairment, as well as current limitations in the field of stroke and executive function research.

Executive function is an umbrella term that includes cognitive processes such as decision-making, impulse control, attention, behavioral flexibility, and working memory. Each of these processes depends largely upon monoaminergic (dopaminergic, serotonergic, and noradrenergic) neurotransmission in the frontal cortex, striatum, and hippocampus, among other brain areas. Traumatic brain injury (TBI) induces disruptions in monoaminergic signaling along several steps in the neurotransmission process - synthesis, distribution, and breakdown - and in turn, produces long-lasting deficits in several executive function domains. Understanding how TBI alters monoamingeric neurotransmission and executive function will advance basic knowledge of the underlying principles that govern executive function and potentially further treatment of cognitive deficits following such injury. In this review, we examine the influence of TBI on the following measures of executive function - impulsivity, behavioral flexibility, and working memory. We also describe monoaminergic-systems changes following TBI. Given that TBI patients experience alterations in monoaminergic signaling following injury, they may represent a unique population with regard to pharmacotherapy. We conclude this review by discussing some considerations for pharmacotherapy in the field of TBI.

Fixating on the present moment rather than considering future consequences of behavior is considered to be a hallmark of drug addiction. As an example, cigarette smokers devalue delayed consequences to a greater extent than nonsmokers, and former smokers devalue delayed consequences more than nonsmokers, but less than current smokers. Further, cigarette smokers have higher norepinephrine levels than nonsmokers, which is indicative of poor future health outcomes. It is unclear how duration of cigarette smoking may impact these associations. The current secondary analysis of publicly available data investigated whether extent of future thinking is associated with smoking duration, as well as norepinephrine level, in a large national US sample (N = 985) of current, former, and never smokers. Individuals scoring lower on future thinking tended to smoke for longer durations and had higher norepinephrine levels relative to individuals scoring higher on future thinking. In addition, duration of cigarette abstinence interacted significantly with future thinking and smoking duration for former smokers. Specifically, the mediation relationship between future thinking, smoking duration, and norepinephrine level for former smokers was strongest at shorter durations of cigarette abstinence and decreased as a function of increasing duration of cigarette abstinence. Overall, results from this study suggest the potential importance of implementing smoking cessation treatments as early as possible for smokers and support future thinking as a potential therapeutic target for smoking cessation treatment.

RATIONALE: Nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs), and mecamylamine, a nonselective nAChR antagonist, attenuates effects of nicotine on delay discounting in some rat strains; whether nicotine’s attenuation is specific to nAChR antagonism is unknown. OBJECTIVE: During experiment 1, we evaluated dose-dependent effects of nicotine on delay discounting of pair-housed Lewis (LEW) and Fischer 344 (F344) rats. During experiment 2, we examined the sensitivity of nicotine’s effects on delay discounting to pharmacological antagonism of nAChRs or muscarinic AChRs (mAChRs). MATERIALS AND METHODS: Male LEW and F344 were trained to choose between one food pellet delivered immediately and three food pellets delivered after an increasing delay. During experiment 1, saline and nicotine (0.1–1.0 mg/kg) were tested acutely. During experiment 2, mecamylamine (0.25–1.0 mg/kg) or a nonselective mAChR antagonist, scopolamine (0.01–0.056 mg/kg), was administered prior to nicotine administration. RESULTS: Nicotine dose dependently reduced delay discounting for both rat strains, and no strain differences were observed (ΔAUC = + 107% for 1.0 mg/kg and + 69.6% for 0.3 mg/kg relative to saline). At some doses, pretreatment with mecamylamine (range ΔAUC = − 27.6 to − 7.3%) or scopolamine (range ΔAUC = − 0.74 to − 51.6%) significantly attenuated the nicotine-induced reduction in some measures of delay discounting for both strains. CONCLUSIONS: Results from experiment 1 suggest that when LEW and F344 are pair housed, there are no strain differences in delay discounting in response to nicotine. Results from experiment 2 suggest that attenuation of nicotine’s effects on delay discounting may not be specific to nAChR antagonism.

Snus tobacco characteristics may attract non-tobacco users, including relatively low, but pharmacologically active, doses of nicotine. Lower nicotine doses may limit adverse drug effects while also producing a physiologically active response.This pilot study is the first to profile the acute effects of snus on physiological and subjective assessments in a sample of never-tobacco users.Eleven never-tobacco users (five women;100 uses/lifetime) were recruited from the community via university-approved advertisements. Using a within-subject design, participants consumed six pouches in ascending dose order (0, 1.6, 3.2, 4.8, 6.4, and 8.0 mg nicotine) within one session. The start of each snus bout was separated by 45 minutes, and pre- and post-pouch assessments included ratings of drug effects and physiological response.The average heart rate and systolic blood pressure increased significantly from pre- to post-pouch use as a function of dose, though these increases were reliable for 8.0 mg nicotine only (p.05). Collapsed across time, diastolic blood pressure was significantly higher for 8.0 mg nicotine than for all other doses (p.05). Subjective ratings for "excessive salivation" and "satisfying" increased significantly from pre- to post-pouch use (p.05), independent of dose.Significant increases in physiological response at some doses suggest that users were exposed to pharmacologically active doses of nicotine. The lack of reliable subjective effects may be the product of the dosing regimen or the relatively small sample size. Findings highlight the need for identification of doses of snus that may promote abuse among naïve users.